MOA spasmodic

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					                  MOA                                    CLINICAL SIGNS                                    MANAGEMENT                                  PROGNOSIS   TOXICOKINETICS
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CHOLILNERGIC AGONISTS                                    -                                                 -                                           -           -

                  -                                      -                                                 -                                           -           -
Tobacco           -   NORNICOTINE more toxic than        -  Emesis early (product irritating to            -   bathe if dermal exposure                -           -   contains anabasine (teratogen)
                      NICOTINE ( but less abundant)         stomach, nicotinic effects on CRTZ &           -   emetic if early & appropriate                       -   livestock poisoning not common
Nicotiana         -   LOBELINE weaker than nicotine         emetic center)                                 -   AC/SC                                               -   entire plant contains toxic principle
tabacum           -   Mimic ACh at sympathetic &         Early                                             -   Atropine for parasympathetic effects
                      parasympathetic ganglia, NMJ, &    - excitation, tachypnea, salivation, emesis       -   IV fluids                                           Nicotine
Lobelia spp.          nicotinic recepors in CNS             diarrhea                                       -   Artificial respiration                              - poor absorption from stomach
                                                         Late                                              -   Urinary acidification (ION TRAPPING)                - well absorbed from intestine, resp
                  2 phases                               - muscle weakness, depression, twitching,         -   Avoid oral antacids (may enhance                       tract, skin
                  - Low dose – depolarization & stim        slow resp, resp aparalysis, collapse,              absorption from gut)                                - Alkalinization enhances absorption
                     receptors similar to ACh               coma, cyanosis, cardiac arrest, death                                                                  - May undergo enteroheptaic recirc
                  - High dose – stimulation followed                                                       Control                                                 - Primary metabolite = cotinine (lower
                     by blockage at autonomic ganglia    Diagnosis                                         - Provide adequate food                                    potency than nicotine
                     & myoneural jxns of skeletal m.     detect nicotine in urine, blood, liver, kidney,   - Prevent accidental exposure
                     (depolarizing blockade) death      GI                                                - Herbicides may be useful in controlling
                     due to resp fail                                                                        plants
                  -                                      -                                                 -                                           -           -
Poison Hemlock    - 5 principle alkaloids: coniine, N-   -  Muscular weakness, trembling, ataxia,          - Early: decontaminate (emetic & AC/SC)     -           -   don’t confuse w/ water hemlock
                     methyl coniine, gamma-coniceine,       slobbering, rapid pulse, dilated pupils,       - Symptomatic & supportive                                  (poison hemlock leaf veins go to the
Conium               conhydrine, pseudoconhydrine           frequent urination & defecation                                                                            leaf tip)
maculatum         - Nicotinic-type alkaloids            - Musty mousy odor on breath & in urine           Control:                                                -   all parts of the plant (inc. seeds) are
                     neuromuscular blockers              - Initial stimulation followed by analgesic-      - Keep animals away from plants during                      toxic
Spotted hemlock   - Initial stimulation, followed by        like depression                                  prime growth (spring)                                 -   confused w/ parsley & wild carrots
                     depression of autonomic ganglia     - Death due to resp fail                          - Provide adequate nutrition
Spring plant in      & skeletal m.                       Pigs,goats, sheep, cattle                         - herbicides
Illinois          - Teratogenic effects                  - Temporary partial loss of vision due to
                                                            nictitating mem covering pupil

                                                         - History & signs
                                                         - Possible detection in GI, blood, urine
                  -                                      -                                                 -                                           -           -
Lupine            -   Piperidine & Quinolizidine         Sheep                                             -   Symptomatic & supportive                -           -   seeds & seed pods contain highest
                      alkaloids                          - Labored breathing & depression                                                                              conc of alkaloids
Lupinus spp       -   Bind to ACh nicotinic receptors    - Followed by coma & death                        Control                                                 -   seeds have high nutrient content 
                      w/ varying affinities              - May initially exhibit hyperexcitability &       - Keep away from plants                                     may be sought out when other forage
Western US        -   Initial stim followed by              violent behavior                               - Adequate, nutritious diet                                 scarce
                      depolarizing blockade              Cattle                                            - herbicides
                  -   Anagyrine is teratogenic           - Hypersalivation, burxism
                                                            (grinding/clenching teeth), ataxia,
                                                            muscular weakness, recumbency
                                                         - Death due to resp fail

                                                         - History, signs
                                                         - Possible detection – GI, blood, liver,
                  -                                      -                                                 -                                           -           -
Imidacloprid   -  binds to post-synaptic nicotine ACh     Oral:                                           Oral:                                       -   -   insecticide (crops) & flea control
(Advantage)       receptor  prevent binding of ACh       - salivation or vomiting w/in minutes           - dilution w/ milk or water                     -   oral  quick & almost completely
               Insect                                     - oral ulcers possible in cats dosed orally     - NPO if vomiting                                   absorbed
               - persistent activation  accum ACh           w/ spot-on treat                             Dermal hypersensitivity                         -   dermal  minimal to NO systemic
                  & overstim cholinergic synapses        Dermal                                          - Bathe w/ liquid dish washing detergent            absorb
                  hyperexcitation, convulsions,           - dermal hypersensitivity (redness, pruritis,   - Antihistamines and/or steroids may be         -   Very lipophilic  resides in fat
                  paralysis, death                           alopecia) w/in hours                            needed in extreme cases                      -   WIDE margin of safety
               - Interruption of nerve transmission                                                                                                      -   Degraded in liver to active metabolite
                  paralysis & death                       -   nicotinic signs not expected (wide                                                          -   Elim  urine & feces
               - Kills fleas on contact (different from       safety margin)
                  IGR & developmentinhibiots)  has                                                                                                       -   Low toxicity  there are higher
                  an effect on adult fleas                                                                                                                    conc nicotinic ACh receptors in
                                                                                                                                                              insect nervous tissue than
                                                                                                                                                          -   Higher affinity for insect than
                                                                                                                                                              vertebrate receptors
                                                                                                                                                          -   Safe for use in pregnant & nursing
                                                                                                                                                          -   toxic to bees, aquatic invertebrates,
                                                                                                                                                              game birds, fish
               -                                          -                                               -                                           -   -
AGENTS THAT CAUSE PARALYSIS                               -                                               -                                           -   -

               -                                          -                                               -                                           -   -
Black Widow    -   ALPHA-LATROTOXIN binds to              -   Dull numbing pain at sight of injection     -   Respiratory, cardiac, & pain            -   -   shy spiders – only bite when
Spiders            glycoprot or gangliosides on               of venom                                        management                                      threatened
                   neuromuscular presynaptic mem         -   Muscle cramps, muscle fasciculations,       -   Pain  opioids or benzodiazepines,          -   only FEMALE capable of
(Latrodectus       cationic ion channels remain open          tonic-clonic convulsions                        steroids                                        envenomation (both equally
mactans)       -    depolarization & release of NT       -   Sweating, excess salivation, flaccid        -   Methocarbamol and/or calcium                    venomous – male jaws to small to
               -   Result = Release & depletion of ACh        paralysis                                       gluconate for muscle fasciculations &           penetrate)
               -   Initial stim  then stops              -   Weakness w/ dyspnea followed by                 weakness                                    -   all mammals sensitive
                                                              paralysis may occur w/in 6 hrs in acute     -   Antivenin (Merck) – test dose               -   CATS = most sensitive
                                                              case                                            intradermally to monitor
                                                                                                              hypersensitivity  IV over 15 min           -   medium sized spider, shiny black
                                                          Most are self limiting & clinical signs                                                             abdomen w/ red hourglass or red
                                                          resolve w/in 4-6 hrs                                                                                spots
                                                                                                                                                          -   in warmer parts of US
               -                                          -                                               -                                           -   -
Botulism           3 main routes of exposure                    -   Myasthenia, inability to swallow           -   Remove source (feed or gut contents)      -   Guarded to   -   anaerobic gram+ spore forming rod
                   - ingestion of PREFORMED TOXIN               -   Progressive muscle paralysis               -   Antitoxin                                     poor         -   commonly found in environ, esp soil
Clostridium           (cattle, horses, birds) – due to contam   -   Muscle weakness begins in                  -   Antibiotics (penicillin)                                   -   heat labile toxin
botulinum             of food or water w/ decaying                  hindquarters & progress to                 -   Wound debridement                                          -   spores resistant to drying
                      carcasses, or improperly                      forequarters – head & neck affected        -   Symptomatic & supportive (resp
Limber neck           prepared/stored food                          last                                           support)                                                   -   **Most common source of toxin =
(waterfowl)        - ingestion of SPORES                        -   Death due to resp paralysis                                                                                   carrion
                      (toxiooinfectious botulism or shaker      -   No effect on CNS (still alert)             Control                                                        -   waterfowl: decaying vegetation &
Shaker foal synd      foal synd)                                                                               - Vax                                                              invertebrates in flooded
(foals)            - contam of WOUNDS w/ spores (deep           Diagnosis                                      - Ensure clean, properly processed &                               areas/stagnant water
                      puncture wounds or surgical contam)       - Clin signs, analysis                           stored feed                                                      (maggots=vector)
                                                                - Analysis of serum, GI, feedstuffs for        - Prompt & proper disposal of carcasses                        -   cattle: carrion incorporated into feed,
                   -   BOTULINUM TOXIN enters                      preformed toxin                                                                                                osteophagia (eating of bones of dead
                       presynaptic mem of cholinergic           - Mouse inoculation most sensitive                                                                                animals – assoc w/
                       nerve endings via receptor mediated      - ELISA for type C                                                                                                hypophosphatemia)
                       endocytosis                                                                                                                                            -   horses: extremely sensitive (carrion
                   -   Intracellularly toxin disrupts actions                                                                                                                     in feed or “toxicoinfectious botulism”
                       necessary for ACh vesicle docking,                                                                                                                         – foals <8mos, typically 2 mos)
                       fusion, & release into synapse
                   -   Result = inhibition of degranulation
                       or release of ACh granules
                   -   Irreversible binding by small
                       number of toxin molecules 
                       IRREVERSIBLE cessation of all
                       cholinergic transmission
                   -   Death from Resp fail
                   -                                            -                                              -                                             -                -
Larkspur           -   METHYLLYCACONITINE =                     -   Sudden death                               -  Remove from source                         -                -   Sources: Diterpenoid alkaloids
                       Neuromuscular blocking (curare-          -   Signs primarily NERVOUS:                   -  Handling may exacerbate distress                                (plants in western US)
Delphinum spp          like) agent                                  hyperirritability, confusion nausea        -  Relieve bloat by stomach intubation or                      -   DAN (14-deactylnudicauline) most
                   -   Acts at postsynaptic nicotinic,          -   Mild muscle tremors, stiffness,               trocharization                                                  toxic
                       cholinergic receptors in CNS & NMJ           weakness                                   Increase ACh in synapse by inhibiting                          -   MLA (methllycaconitine) most
                   -   If sufficient receptors blocked         -   Constipation, bloat, oral irritation,      AChE                                                               abundant
                       ACh cannot bind & muscle does not            vomit (or regurgitation), salivation       - Physostigmine (not approved in cattle)                       -   Well absorbed orally
                       contract                                     followed by dry mouth                      - Neostigmine (approved in cattle)                             -   Minimal rumen degradation
                                                                -   Collapse, prostration                      - Short lived effects  retreatment
                                                                -   Inhalation pneumonia common in                                                                            -   CATTLE most susceptible – cattle
                                                                    recumbent animals as a result of vomit     Control                                                            cholinergic receptors more
                                                                -   Convulsions                                - Avoid access to plants (not practical)                           susceptible to diterpeniod alkaloids
                                                                -   Death due to resp paralysis or bloat       - Avoid grazing when plants are most toxic                         than those of sheep
                                                                -   Fatalities usu w/in 3-4 hrs of ingestion     (flowering)                                                  -   Sheep tolerate 4-5 x more than cattle
                                                                    of a fatal dose                            - Provide adequate feed & forage                               -   Horses less susceptible than cattle
                                                                                                               - Graze area w/ sheep prior to introduction                    -   Alkaloid conc highest in young,
                                                                                                                 of cattle                                                        growing plants just prior to & during
                                                                                                               - Herbicide to dense patches                                       flowering
                                                                                                               - Aversion = lithium chloride
                                                                                                               - Biological control = larkspur myriad
                   -                                            -                                              -                                             -                -
Tick Paralysis     -   Neurotoxin                               -   Ticks feeding for 5 or more days             -   Removal of tick  marked                    -   -   Female ticks secrete Neurotoxin from
                   -   May have short-lived immune response     -   Ascending paresis/paralysis                      improvement w/in 24 hours followed                  salivary glands when feeding
                   -   May interfere w/ ACh syn or liberation   -   Animals retain pain sensation                    by complete recovery w/in days                  -   Dermacentor andersonia, D.
                       at motor end plate                       -   Retain tail wag                              -   Examine ear canals, ear folds, &                    variabilis, Ixodes, Amblyomma
                   -   Results in LMN paralysis                 -   Death from resp muscle paralysis                 interdigital areas  remove all ticks
                                                                -   Removal of tick  rapid recovery             -   Even when no ticks are found, but               -   CATTLE & SHEEP common – NW
                                                                                                                     signs still suggest tick paralysis  tick           US
                                                                                                                     dip solution indicated                          -   Horses less common
                                                                                                                 -   Assist respiration in severe cases              -   Paralysis can result from 1 female
                                                                                                                 -   Treat w/ Fipronil (Frontline) to                    tick
                                                                                                                     prevent infestation                             -   More common in DOG
                                                                                                                                                                     -   Rare in cat
                                                                                                                                                                     -   Wildlife rare
                   -                                            -                                                -                                               -   -
AGENTS AFFECTING SKELETAL                                       -                                                -                                               -   -

                   -                                            -                                                -                                               -   -
Hybrid Sudan       Toxic princ = Β-CYANOALANINE                 -   Ataxia, esp noticeable when horses           -   Animals may slowly recover if removed       -   -   prolonged ingestion of pasture or hay
Johnson Grass      (LATHYROGEN)                                     backed or turned. May sit on hind                from source before cystitis & ataxia                containing sorghums
                   - prolonged ingestion of pasture or hay          quarters or fall over                            become complicated by serious                   -   HORSES especially sensitive
Sorgum spp           containing sorghums                        -   Paralysis of urinary bladder results in          secondary problems                              -   cattle, sheep may be poisoned
                   - conversion of cyanide to β-                    continual dribbling of urine  scald,        -   Complete recovery seldom occurs once            -
Equine Cystitis-     cyanoalanine,a known lathyrogen                hair loss. Cystitis may develop                  severe signs develop
ataxia syndrome    - lathyrogens affect normal                      progress to an ascending nephritis.          -   Antibiotics & supportive care
                     development of nervous tissue                  Urine becomes thick & opaque.
Sorghum cystitis   - β-cyanoalanine interferes                      Bladder palpates as enlarged & flaccid
                     w/glutamate receptors in CNS              -   Paralysis of perineum  lips of vulva
                     causing influx of Ca into cells  cell         stay open resulting in vaginitis
                     death                                      -   Loss of tone to rectum  fecal
                   - Result: neuronal degeneration &                impaction & constipation
                     demyelinization of peripheral nerves       -   Flaccid paralysis of tail

                                                                - Hx of exposure & clinical signs
                                                                - Differentials: EHV-1, EPM, Viral
                                                                   encephalitis (cystitis not common)
                                                                - Postmorterm: severe ulcerative
                                                                   necrotizing urethritis & cystitis extending
                                                                   to pyelonephritis. Degeneration &
                                                                   demyelination of axons in spinal cord
                   -                                            -                                                -                                               -   -
Hydrogen sulfide   Direct mucosal irritant                     -   see MOA                                  -   Remove from area                      -   -   produced by anaerobic bacterial
(H2S)              - Local inflam of eye & resp tract                                                       -   Fresh air, oxygen, artificial resp            decomposition of Sulfur containing
                   - Uniform irritation throughout resp        Diagnosis                                    -   Symptomatic & supportive for pulm             organic matter
                      tract, esp deeper pulm tissues           - Hx of manure pit agitation & acute death       edema                                     -   distinctive odor of rotten eggs
                      (bronchcioles & alveoli)  pulm                                                                                                     -   most common hazards are liquid
                      edema                                                                                 Control                                           manure holding pits (H2S
                                                                                                            - Remove animals when pit is agitated             produced in pit  rapid release
                   High conc: systemic effects, esp cartotid                                                - Provide adequate ventilation, agitate           when agitated)
                   body chemoreceptors                                                                        slowly                                      -   usu. SWINE affected
                   - Stim chemoreceptors  excessively                                                      - Observe animals when agitation is           -   occas. poultry & cattle
                      rapid breathing (hyperpnea)                                                             started, stop if any signs develop          -   H2S also assoc w/ natural gas &
                   -  Depletion of CO2 content in blood                                                    - DO NOT ATTEMPT TO                               crude oil prod & coal deposits
                      (acapnia)                                                                               IMMEDIATELY RECULE ANIMLS
                   -  Period of respiratory inactivity                                                       OR ENTER PITS (EVEN EMPTY
                      (apnea)                                                                                 PITS) humans can quickly become
                   - if CO2 does not reaccum in blood                                                        victims
                      spontaneous respiration may not
                      occur  death from asphyxia
                   -                                           -                                            -                                         -   -
Chlorphenoxy       - 2,4-D                                     -   Walking through treated lawns, or        -   bath if dermal exposure               -   -
herbicides &       - 2,4,5-T                                       eating freshly treated grass will only   -   NPO if vomiting
Dicamba            - Contaminated w/ chlorinated                   result in mild GI upset requiring not
                      dibenzodioxins – Agent Orange                specific treatment
                                                               -   Experimentally dosed dogs developed
                                                                   muscle memb irritability & rigidity
                                                               -    Hesitancy to move, rigidity, ataxia,
                   -                                           -                                            -                                         -   -
Ionophores   -   selective ion transport depending          -   Function of excitable tissues affected:   -   Early decontam – emesis & AC/SC     -   If potential   Sources
                 upon specific ionophore (primarily             neurological, musculoskeletal, cardiac,   -   Vit E & Se  minimize secondary         for            - research (ion transporters thorgh
                 Na, K, Ca)                                     sm. Muscle                                    oxidative damage                        myocardial        biological mem)
             -   Ionophore transport proceeds down          -   Death w/in 24 hrs or delayed for weeks    -   IV fluids +/- Bicarb for acidosis       damage        - anticoccidials (chickens, turkeys,
                 conc gradient (btwn                                                                      -   Minimize stress                         poor to           sheep, quail)
                 extracellular/intracellular &              Horses                                        -   Symptomatic & supportive                guarded        - growth promotants in cattle (↑feed
                 estraorganelle/intraorganelle)             - Initial feed refusal (may still eat hay)    -   Treatment often unrewarding         -   Horses not        efficiency, shift VFAs from acetic &
             -   Weakly acidic ionophores complex           - Weakness, ataxia, incoordination,                                                       safe for          butyric to propionic, control bloat,
                 w/ cations & maintain neutral                tremors, stumbling, exaggerated                                                         riding            lactic acidosis, prevent acute bovine
                 charge, allowing transmem                    stepping, hesitance to move or turn,                                                                      pulm emphysema & edema
                 movement                                     tachycardia, congested mucous mem,                                                                     - lasalocid, monensin, narasin,
             -   Once across mem, must again                  hypotension, dyspnea, hyperpnea,                                                                          salinomycin, laidlomycin proprionate,
                 complex w/ another cation to return          sweating, recumbency                                                                                      maduramicin
             -   Result: net cellular imbalance of          - Death often w/in first 24 hrs
                 cations, (esp mitochondria)               - Delayed signs due to residual cardiac                                                                  -   absorption variable, signs occur w/in
                 affecting ATP production                     damage: unthriftiness, poor                                                                                hours
                                                              performance, poor exercise tol,                                                                        -   wide distribution
                                                              arrhythmias, pitting edema,                                                                            -   extensively metabolized
             Clin Path                                        hyperpnea, or sudden death (even mos                                                                   -   rapid biliary elim ( No renal elim)
             - Not markedly altered until just prior to       after exposure)
                death                                                                                                                                                -   toxicity depends on species &
             - Muscle &/or liver damage                     Cattle                                                                                                       particular ionophore
             - Electrolyte abnormalities                    - Earliest: diarrhea, reluctance to eat                                                                  -   HORSES esp. sensitive to monensin
                                                               concentrate portion of diet                                                                               (rumensin)
                                                            - Followed by: general anorexia,                                                                         -   Toxicity enhanced by compounds
             Lesions                                           depression, muscle tremors, weakness,                                                                     competing for metabolism w/
             - More likely seen if animal survives >24         incoordination, ataxia, tachycardia,                                                                      ionophores (tiamulin, ethoxyquin)
                hrs                                            tachypnea, labored respiration, watery                                                                -   Poisonings can occur w/ ingestion by
             - Absence of lesions does not rule out            diarrhea, rumen atony, dehydration,                                                                       non-target species (contamination,
                toxicosis                                      death                                                                                                     feed mixing errors), or feeding
             - Horse: epicardial & endocardial              - Development of CHF                                                                                         excessive dietary conc in target
                hemorrhage, paleness or pale streaking      Sheep                                                                                                        species
                of ventricual myocardium, myocardial        - Similar to cattle                                                                                      -   Susceptible species: horses, cattle,
                necrosis, ↑myocardial friability, loss of   Pigs                                                                                                         sheep, turkeys, pigs, dogs, cats,
                heat tone, hydropericardium,                - Stiffness, tremors, reluctance to move,                                                                    rabbits, deer, guinea fowl, ostriches,
                hydrothorax, ascites                           knuckling, diarrhea, anorexia,                                                                            chickens
             - Cattle & Sheep: paling of myocardium,           lethargy, ataxia, dyspnea, recumbency,
                myocardial streaking, petechia &               myoglobinuria, death
                ecchymosis of myocardium, enlarged          Dogs
                hearts, pulm congesion, pulm edema,         - Depression, weakness, ataxia, paresis,
                hepatic congestion & occasional                myoglobinuria, recumbency,
                hepatomegaly, streaking & hemorrhage           paraplegia, quadriplegia, dysuria, fecal
                of skeletal muscles, pale skeletal             & urinary incontinence, anorexia,
                muscles                                        constipation, weight loss, dyspnea
             - Pigs: white areas w/in skeletal muscle       Cats
                gropus, hydorpericardium, pulm              - Weakness, paresis, paralysis,
                congestion & edema, skin congestion,           dysphonia, loss of spinal reflexes w/
                mottling of epicardium & myocardium            intact conscious pain perception,
             - Cats: paling of myocardium                      dyspnea, death
             - Dogs: NO gross lesions
                                                            - Based on Hx & clin signs
                                                            - Test feed for inophores
                                                            - Tests on tissue difficult to perform &
                                                            - ECG abnormalities - inconsistent
                 -             -                                           -                                         -                 -
Macadamia nuts   -   unknown   usu seen by 12 hrs                          -   supportive                            -   excellent     Sources
                               - weakness, Vomiting, depression            -   keep In warm, protected environment   -   complete      - Hawaiian trees – Macadamia sp
                                  ,ataxia, tremor, hyperthermia (104),         until signs resolve                       recovery in   - Jars of roasted nuts
                                  lameness, stiffness, inability to rise   -   enema may hasten recovery                 48 hrs        - Nut is 75% oil
                               - rear legs more severely affected than
                                  fore legs                                                                                            -   Only reported in DOGS
                               - no pancreatitis develops
                               - signs resolve by 24-48 hrs w/ only
                                  supportive treatment
                 -             -                                           -                                         -                 -
AGENTS CAUSING ACIDOSIS OR FEVERS                                                                               -                                          -                      -
Ethylene Glycol    ETHYLENE GLYCOL                             -   3 stages: severity & time course of signs    Asymptomatic                                                      sources
                   - CNS depression (greater than                  highly dependent upon dose & species         - Emesis (no contrainidcatinos & very recent < 1 hr exposure)     - radiator antifreeze (95%
Antifreeze            ethanol)                                 -   CATS more sensitive than dogs                - Gastric lavage                                                     ethylene glycol)
Coolant            - Diuretic effect – PU/PD                                                                    - Keep anesthesia as light as possible                            - “safe” antifreezes – contain
Radiator coolant   - GI irritant – V/D                         Stage 1 – Neuro & GI signs                       - FLUIDS                                                             propylene glycol
                   Glycoaldehyde                               - Occurs 30 min to several hours post            - AC – minimal effects                                            - windshield washer antifreezes
                   - Short lived – can contribute to CNS          exposure                                      Collect samples: STAT analysis                                       – contain methanol
                      depression                               - CNS: ataxia, depression, drunkenness           - Serum – EG test (dogs only), Chem screen, A/B balance, serum    - (propylene glycol & methanol
                   GLYCOLIC ACID                               - GI: vomiting                                     osmolality                                                         are toxic in large quantities
                   - Longer lived                              - PU/PD due to diuretic effect                   - Urine – consider starting therapy pending lab results              than ethylene glycol)
                   - Major contributor to acidosis             - Dehydration & acidosis                                                                                           - latex & acrylic paints
                   - Nephrosis – damages renal                 - Often not noticed by owner                     Symptomaitc                                                       - diethylene glycol in brake
                      tubules (basement mem intact)                                                             - Assess & stabilize, control seizures                               fluid & paint
                   Glycoxylic acid                             Stage 2                                          - Obtain Hx                                                       - airplane deicers
                   - Short lived – little effect on clinical   - 12-24 hrs post exposure                        - Collect samples: chem. screen, UA, A/B balance, EG test
                      signs                                    - severe metabolic acidosis                         (dog<12 hr ingestion), monitor frequently                      -   rapid absorption of GIT
                   OXALIC ACID                                 - resp: tachypnea                                - Correct dehydration – IV diuresis                               -   metabolism begins w/ 2-4 hrs
                   - Combines w/ Ca ions to form               - cardio: tachycardia                            Correct A/B balance                                                   & EG or its metabolites are
                      crystals that precipitate in renal       - may seizure                                    - Correcting acidosis ↑survivability                                  excreted by 24-48 hrs
                      tubules – causes renal scarring &        - symptomatic animals show continiuation         - Monitor & correct when pH<7.2                                   -   **Metabolism of Ethylene
                      fibrosis                                    of stage 1 signs                              - Bicarb replacement amt baased on serial plasma measurements         Glycol is a mulit-step process
                                                               - acute deat <12 hrs after exposure my be        - Bicarb required = 0.3 x BW x base deficit                       -   *metabolism by alcohol
                   Clin Path                                      due to cardiopulm failure (most common        - Ad min IV or IP in dialysate                                        dehydrogenase critical first
                   - Metabolic acidosis - ↓HCO3, pH,              mech of death in exposed cats)                Fomepizole (4-MP, Antizol-Vet)                                        step
                      pCO2                                                                                      -  specifically inhibits alcohol dehydrogenase,                  -   toxic effects due to EG &
                   - Hypocalcemia – precipitates into          Stage 3                                          -  prevents metabolism of EG to toxic metabolites (parent            metabolites
                      kidneys to form calcium oxalate          - Occurs 12-72 hrs post exposure                    cmpd excreted)
                      crystals                                 - Oliguric renal failure                         - DOGS only. Not effective in cat                                 -   DOGS & CATS most
                   - Hyperglycemia                             - Continuation & worsening of previous           - Can’t be used if dog is in renal failure                            commonly exposed
                   - Hyperkalemia                                 stage signs                                   - Doesn’t worsen acidosis, neuro depression, or interfere w/ EG
                   - Azotemia – after 12 hrs or more                                                               test
                   - Urinalysis: isosthenuria, cellular        Diagnosis:                                       - Use 4-MP or Ethanol – NOT BOTH                                  Prognosis:
                      casts, calcium oxalate crystalluria      Woods lamp                                       CRI Ethanol                                                       Dogs
                                                               - Fluorescence on muzzle, paws, Vomit,           -  competes w/ EG for metabolism by alcohol dehydrogenase        - Good if immed decontam &
                   Lesions                                        urine                                            (which also has a higher affinity for ETOH than EG)               treated
                   Gross:                                      Ethylene Glycol Test kit (serum)                 -  prevents metabolism of EG to toxic cmpds (parent cmpd         - Grave if in renal fail
                   - kidneys pale & firm w/ pale               - Cats can be intoxicated below this level          excreted)                                                      - Once in renal fail  treatment
                      streaks, esp at corticomedullary jxn     - Loses sensitivity 12-24 hrs after ingestion    - create 7% son of ETOH                                              focuses on treating ARF rather
                   Histo:                                         due to metabolism of parent cmpd              - 80 proof = 40% alcohol                                             than antidotal therapy
                   - birefringent calcium oxalate              - False positives due to: formaldehyde or        - everclear or medical grade ethanol preferred
                      crystals found in & around                  metaldehyde, glycerin/glycerol (cough         - will cause CNS depression & worsen signs                        Cats
                      proximal & distal convoluted                syrup, charcoal slurries), propylene glycol   - (7% ) / (%ETOH stock) = (mL required) / 1L fluids               All exposures considered guarded
                      tubules                                  Serum osmol gap                                  Pulse ethanol                                                     at best
                   - multifocal degeneration, atrophy &        - Significant elevation w/in 1 hr exposure       - maintain constant blood ethanol level
                      limited regeneration of tubules          - Osmol gap = measured osmolality – calc         - need to monitor animal & adjust
                   - advanced – interstitial fibrosis of          osmolality                                    - 20% ethanol soln
                      renal cortex & mineralization of         - Measured – lab measures by freezing            Ancillary Treat
                      tubular basement mem                        point depression                              - B-vit
                                                               Anion gap (serum)                                - Thiamine
                                                               - Begins to rise 3-6 hrs post exposure           - Pyridoxine
                                                               Post mortem                                      Peritoneal Dialysis
                                                               - Detection of EG in kidney                      - Very effective at removing metabolites
                                                               - Elevated calcium in kidney                     - Also removes ethanol & 4-MP – adjust doses
                                                                                                                - Hemodialysis
                  -                                               -                                          -                                            -                 -
Salicylates       -   Selective COX 1 inhibitor at low            Low dose                                   Asymptomatic or Low dose exposure            -                 Sources
                      doses                                       - GI – Vomit, anorexia, melena             - Decontam – emesis / AC                                       - aspirin (acetylsalicylic acid)
                  -   Non-selective COX at high doses             - ↑ bleeding times                         - Stop any therapeutic aspirin treatment                       - GI products (alka-seltzer,
                  -   COX1 – constitutive isoform found in        - delayed parturition                      - IV fluids                                                       peptobismol-bismuth subsalicylate,
                      all tissues, produced continuously          - signs may be seen at therapeutic doses   - Correct dehydration                                             sulfasalazine, kaopectate)
                  -   COX2 – inducible isoform, not found                                                    - Monitoring: baseline, 48-72 hrs                             - Topical preps of r muscle
                      in most tissues, highly regulated in        High dose                                    CBC, Chem, A/B balance, UA                                      soreness/arthritis (bengay-methyl
                      response to infection or cytokines          - CNS, seizures, coma                      - Anit-emetics                                                    salicylate)
                                                                  - Resp: tachypnea, pulm edema              - GI protectants – Misoprostol,
                  Inhibition of COX inhibits PG syn               - GI: vomit, anorexia, melena                Sucralfate, H2 blocker or proton pump                        -   Rapid oral absorb
                  - Therapeutically ↓PG  ↓inflamm                - Metabolic: fever, metabolic acidosis,      inhibitor                                                    -   Widely distributed
                  - Toxicologically ↓PG  ↓gastro-                   hyperglycemia                           - NPO until vomiting stops for 24 hrs                          -   Acidosis ↑distribution to CNS
                     protection, ↓renal perfusion                 - Blood: ↑ bleeding times, Heinz body                                                                     -   Glycine or glucuronide conjugation
                                                                     anemia in cats                          Severe signs                                                   -   Renal excretion
                  Specifically for aspirin & other salicylates:                                              - Stabilize, seizure control, regulate                         -   Long T ½ in cats
                  - Hyperpyrexia, ↑temp – uncoupbles cell                                                       temp
                     resp in mitochondira                                                                    - Baseline chem., CBC, UA                                      CATS esp sensitive
                  - Aspirin molec can move protons across                                                    - Treat acidosis                                               - Low capacity for glucuronidation
                     inner mitochondrial mem                                                                 - IV fluids                                                    - Likely to receive large doses for body
                  - Mito e-transfer train continues to pump                                                  - Correct elect anomalities                                      size
                     protons out of matrix, but protons can                                                  - May need whole blood if
                     be carried back in by aspirin rather than                                                  hemorrhaging
                     by flowing through ATPsynthetase                                                        - Careful diuresis – monitor urine
                  - Efficiency of cell respiration ↓ from                                                       output & watch for pulm edema
                     normal level  amt of heat prod ↑                                                       - Gastric lavage? – enteric coated pills
                  - Metabolic acidosis, (↓pH) – excess of                                                       may form a concretion, stomach may
                     aspirin (acid)  overwhelm bloods                                                          be vulnerable to trauma
                     bicarb buffer sys                                                                       - Gastric protectants – anti emetics,
                  -                                                                                             misoprostal, sulcralfate, H2
                                                                                                                blocker/proton pump inhibitor
                  -                                               -                                          -                                            -                 -
Hops              -   toxic principle unknown                     -   produces a malignant hyperthermia-     - early emesis, gastric lavage               -   Poor to       -   Sources – spent hops plugs from
                  -   mech unknown                                    like synd in dogs                      - AC/CT                                          guarded           home beer brewing
Humulus lupulis                                                   -   signs can be seen by 3 hrs             - IV fluids to prevent myoglobin or          -   Most          -   Signs can begin by 3 hrs
                                                                  -   initial: agitation, tachypnea, abd        hemoglobin induced renal failure              affected
                                                                      discomfort, hyperthermia (104)         - A/B monitoring & correction                    animals die
                                                                  -   rapid progression: pacing,             - Cooing measures (avoid alcohol)
                                                                      vocalization, painful abd,             - Dantrolene (Dantrium) – direct acting
                                                                      myoglobinuria, profound                   skeletal muscle relaxant (may interfere
                                                                      hyperthermia (108)                        w/ release of Ca form sarcoplamic
                                                                  -   death by 6 hrs                            reticulum)
                  -                                               -                                          -                                            -                 -
RENAL / URINARY TRACT                                           -                                        -                                               -                  -
                    -                                           -                                        -                                                -                   -
General manifestations of Renal Fialure                                                                  Factors affecting Toxicity
                                                                                                          High blood flow to kidney (25% CO)
Clinical Response to Injury                                                                                   o     Renal cortex receives 90% of renal blood flow
 isosthenuria & proteinuria                                                                                  o     Nedulla receives 6-10%
     o    mild damage, may be reversible                                                                      o     Papilla receives 2%
     o    animal will likely appear normal due to reserve capacity of kidney                              Kidney has high metabolic demands (10% of body’s total Oxygen consumption)
     o    usu Not assoc w/ gross or histo lesions                                                             o     Many renal functions rely on active transport mech
 Acute Renal Failure (ARF)                                                                                   o     Toxicant inhibition or damage can result in a variety of abnormalities (kidneys serve to excrete
     o    Severe consequence of nephrotoxicity, often reversible                                               metabolic wastes, metabolism & excretion of xenobiotics, regulation of extracellular fluid vol,
     o    ↓GFR, ↑BUN & creatinine, oliguria/anuria, proteinuria, aminoaciduria, glucosuria                     maintenance of elect compostion)
     o    V/D, dehydration, lethargy, metabolic acidosis, hyperphosphatemia                               Protective characteristics of kidney
     o    Kidneys painful on palpation                                                                        o     Detoxificiation enzymes – proximal tubular epithelial cells
     o    Swollen & excessively moist kidneys on gross necropsy                                               o     Ability to regenerate – dependent upon condition of basement mem
     o    Some toxicants cause darkening of parenchyma                                                        o     Reserve capacity – 50-70% of neprons must be damaged before elevations in BUN & creatinine
     o    Tubule crystal deposits & parenchymal mineralization - linear streaks                                occur
     o    Papillary necrosis - zone of pale ischemic tissue w/in inner papilla
 Chronic Renal Failure (CRF)                                                                            Regional susceptibility & responses to toxicity
     o    Prolonged renal damage following exhaustion of reserve capacity                                 Glomerulus
     o    Polyuria, isosthenuria, ↑BUN & creatinine, oral ulcerations                                         o    Not commonly affected by toxicants
     o    End-stage kidneys – smaller than normal & irregular shape                                       Proximal tubule
     o    Mulit-focal fibrous adhesions – difficult to peel off renal capsule                                 o    Most sensitive portion of nephron to hypoxia & toxicity
     o    Intersitital fibrosis – radiating pale streaks                                                      o    Highly involved in active transport
                                                                                                              o    High in mixed function oxidases – metabolism of xneobiotics
Hisotpath                                                                                                     o    Tubular necrosis (nephrosis) – most common form of toxicant induced renal damage
 Mesangioloysis                                                                                          Renal papilla
     o    Necrosis & destruction of glomerulus                                                                o    Very susceptible to decreases in local blood flow
     o    Not common sequele of nephrotoxicosis                                                           Lower Urinary tract (ureters, bladder, urethra)
 Nephrosis                                                                                                   o    Resistant to toxicant induced injury
     o    Acute tubular necrosis                                                                              o    Less metabolically active than proximal tubules & has less contact time w/ urinary wastes
     o    Degeneration & necrosis of proximal convoluted tubular epithelium  followed by sloughing           o    Transitional epithet lining the LUT may become inflamed, ulcerated, or neoplastic
     o    Result is dilated tubular lumens filled w/ granular or cellular casts
 Mineralization
     o    Due to a primary toxicosis or secondary to renal failure
     o    Calcium salts deposit along basement membranes such as those lining the renal tubules, blood
          vessels, glomerular tuft & capsule
     o    As mineralization progresses, tubular epithelial lining becomes mineralized, degenerates,
          sloughs & causes tubular obstruction
 Papillary necrosis
     o    Due to ischemia of inner portion of renal medulla
     o    May undergo complete coagulative necrosis & partial mineralization
 Lower Urinary tract
     o    Cystitis, mucosal hemorrhages, or hyperplasia & neoplastic transformation of epithelium

General Management for Renal Failure
 Decontaminate GIT
 Obtain baseline CBC, Chem, UA (recheck daily)
 Fluids – rehydrate as needed & 2X maintenance
 Diuretic (furosemide) to start kidney output if patient is oliguric or anuric
 Peritoneal dialysis as needed, or hemodialysis if equipped
 Monitor elect, A/B balance
 Monitor lung fields to prevent over-hydration
 Monitor body weight to prevent over-hydration
                  -                                              -                                       -                                               -                  -
Zinc              Hemolytic mech In DOGS not completely          GI                                      -   Decontaminate – if object still in gut      -                  -   pennies minted after 1982 (97.5%
              understood                                  -   profuse vomiting (self limiting) w/ zinc       induce emesis, or retrieve via                             zinc)
              - may be related to inhibition of               oxide ointments                                endoscope or surgery.                                  -   cage nuts & bolts, galvanized
                 sulfydryl-containing enzymes                                                            -   Track progress of object w/ rads                           metals
              - possible: zinc inhibition of specific     Intravascular hemolysis                        -   AC won’t work                                          -   chronic ingestion of Zinc oxide
                 RBC enzymes, direct damage to RBC        - pallor, weakenss, tachycardia,               -   Chelation w/ CaEDTA, D-                                    ointments
                 mem, damage to erythrocytic                 hemoglobinmia, hemoglobinuria,                  penicillamine, BAL (usu not necessary)
                 organelles, immune mediated                 icterus                                         – serum Zn levels decrease rapidly                     -   absorption – proximal SI
                 destruction from hapten formation,       - regenereative hemolytic anemia,                  once object is removed from gut                        -   rapid distribution to biologically
                 increased susceptibility of RBC to          leukocytosis, neutrophilia                      (succimer not effective)                                   active sites
                 osicateive damage by other endogenous    - anisocytosis, polychromasia, basophilic      -   Fluids                                                 -   excreted via bile, intestinal mucosal
                 or xenobiotic agents                        stippling, nucleated RBCs, Heinz            -   Alkalinize urine – toxicity of heme to                     secretions, & pancreatic fluid
                                                             bodies                                          proximal tubular cells is reduced in
              Direct GI irritant (acute zinc oxide                                                           alkaline environment
              exposures)                                  Hemoglobinuric ARF
                                                          - oliguria, anuria, azotemia, urinary
              Hemoglobinuric acute renal failure (3         casts
              - vasoconstriction – Nitric oxide           Mixed Neuro signs
                involved                                  - lethargy, depression, weakness
              - tubular obstruction – precip of heme
                pigments may be promoted in acid
                urine  cast formation &
                intratubular obstruction                  Diagnostics
              - direct cytotoxicity – heme absorbed       Ante mortem
                by proximal tubular epith cells,          - Serum zinc conc – collect in royal blue
                catabolites responsible for                  top tubes & rubber free syringes
                cytotoxicity (oxidative denaturation      - Evidence of hemolysis –
                of lipid, DNA, mitochondrial,                hemoglobbinemia, hemoglobiuria
                cytoskel, other prot)                     - Evidence of metallic object in gut –
                                                             rads, vomit
              Lesions                                     - Chronic exposure to ointments
              - Grossly nonspecific – icterus,            Post-mortem
                 spenlomegaly, red-brown kidneys,         - Liver & kidney zinc conc
                 hemorrhageic gastroenteritis             - Gross & histo on liver, kidneys
              Histo – proximal tubular degeneration &
              necrosis, hepatic hemosiderosis w/
              vacuolar degeneration, hepatocellular
              -                                           -                                              -                                            -             -
Vitamin K3    - cytoxicity due to formation of reactive   -   uremia, death                              -   no specific antidote                     -   guarded   -   HORSES poisoned at therapeutic
injectable       Oxygen species & oxidative stress        -   renal tubular nephrosis                    -   symptomatic treat for renal failure                        doses given parenterally
                                                                                                                                                                    -   Used to treat epistaxis
              -                                           -                                              -                                            -             -
Blister Beetles   -   toxic principle = CANTHARIDIN             Low Dose                                        -   may require 3-10 days                      -   guarded to    -   usus HORSES
                  -   Rapid absorb from GIT & excreted in       - Depression, anorexia, discomfort              -   prevent further exposure (remove               poor          -   also, cattle & sheep
(Epicauta sp)         urine                                                                                         source, change diet)
                  -   Mucosal surfaces vulnerable to vesicant   High Dose                                       -   enhance fecal & urinary elimination                          -   CANTHARIDIN – bicyclic terpenoid
                      action  vesicles, ulcers, erosions       - Restlessness, depression, tachypnea,              (A/C may bind cantharidin, mineral oil                           vesicant found in hemolymph &
                  -   May interfere w/ oxidative enzyme sys        tachycardia                                      may hasten movement though GIT –                                 genetalia of blister beetles
                      affecting active transport across         - Mucosal ulcers in mouth, stomach,                 admin separately or oil will bind A/C)                       -   Envrionmentally stable – potent
                      mitochonddiral mem                           GIT, ureters, bladder, urethera              -   Pain relief – α2 adrenergic agonists,                            irritant & vesicant
                  -   Result: inability to maintain cellular    - Fever, pollakiuria, diarrhea                      butorphanol                                                  -   Texas & Oklahoma
                      fluid balance  acantholysis & vesicle    - ***synchronous diaphragmatic flutter
                      formation                                    (“hiccup” w/ each heartbeat) – related       Fluid therapy                                                    -   Males synthesize toxin, transferred to
                                                                   to hypocalcemia                              - rehydation                                                         females during copulation
                  Lesions                                       - muscle fasciculations                         - dilute serum cantharidin levels (&                             -   Most cases result from ingestion of
                  - No lesions possible w/ sudden death         - shock, death                                     conc passing through kidney)                                      alfalfa hay
                     (very high doses)                                                                          - increase excretion through kidney                              -   ↑ risk when hay is cut & crimped
                  - Hyperemia, ulcerations, erosision           Clin Path                                       - monitor & adjust serum Ca, Mg, &                               -   dead beetles or dried juices from
                     possible theorughout urinary & GI tract    - ↑PCV, ↑ serum protein early followed by          A/B levels                                                        crushed beetles of concern
                  - Possible myocardial necrosis                   ↓ serum prot late, ↑CK, ↓ urine Specific                                                                      -   source of aphrodiasiac “Spanish Fly”
                                                                   gravity, hypocalcemia                        Control
                                                                                                                - feed small square bales to facilitate hand
                                                                   Diagnosis                                      inspection of hay
                                                                   - urine, gut contents – cantharidin          - cut hay before bloom stage or after first
                                                                      analysis (collect samples early due to      frost
                                                                      rapid renal clearance of cantharidin 3-   - cut hay w/out crimping
                                                                      4 days)                                   - avoid wheel traffic on hay
                                                                   - any detection of cantharidin is            - scout fields for beetles before & during
                                                                      significant                                 harvest
                                                                   - beetles or beetle pats found in hay or
                                                                      pelleted feed
                  -                                                -                                            -                                              -                 -
Sulfonamides      -   antimicrobial effects due to inhibition of dihydropteroate synthase                       -   Discontinue & remove source of sulfa       -   Good for      -   various sulfa drugs
                                                                                                                -   Fluids – ensure animals well hydrated          aplastic      -   toxicity varies w/ sulfonamide
                  Toxic mech due to:                                                                            -   Alkalinization of urine (ion trapping)        anemial &
                                                                                                                    enhance removal                                coagulopath   -   all species susceptible
                  precipitation of sulfa (or metabolite) in renal tubules                                       -   Vit K for coagulopathy – monitor coag          y             -   young, dehydrated patients – more
                  - (older sulfas are less water sol & precipitate in acid urine – carnivores)                      panels for animals on prolonged courses    -   Guarded for       likely to develop crystalluria
                  -  oliguria, anuria, hematuria, crystalluria, azotemia.                                          of sulfas                                      renal         -   KCS more likely w/ prolonged
                  - Necropsy – gritty kidneys                                                                   -   Cyclosporine or pilocarpine for tear           dysfunction       therapy
                  inhibition of Vit K producing bact in gut                                                         production – monitor tear production       -   Poor for
                  -  coagulopathy                                                                                                                                 KCS (may
                  - bruising & hemorrhage, prolonged bleeding times                                                                                                be
                  potentiated sulfas (trimethoprim, ormethoprim) may reduce gut folate-producing                                                                   permanent)
                  - insufficient folate to maintain bone marrow progenitor cells  aplastic anemia
                  - leucopenia, thrombocytopenia
                  hypersensitivity or idiosyncratic rxns
                  -  KCS, dermal eruptions, hepatic necrosis, hemolytic anemia & hypothyroidism
                  - Decreased tear prod, blepharospasm, corneal ulcers
                  -                                             -                                               -                                              -                 -
NSAIDS   Therapeutic Mechanism                                             -   Acute toxicity of   -  Decontam (early emesis, AC plus          -   Depends on   Sources
         - 2 isoforms: COX 1 & COX 2                                           ibuprofen in           repeated doses, CT) to remove drug           dose &       - inhibit COX enzymes
         COX 1                                                                 DOGS                   from gut & reduce absorption                 duration     - veterinary preparations
         - constitutive isoform in all tissues                                                     - Baseline renal values & monitor daily     -   Good w/
         - produced continuously, slightly regulated, involved in tissue   Signs                      for 3-4 days                                 prompt &     -   well absorbed from stomach & prox
            homeostatis (production of PG, modulate blood flow             - Vomit,                - IV fluids 2X maintenance                     aggressive       SI
         COX 2                                                                anorexia,               rehydrate, support BP & O2 perfusion,        treat        -   highly prot bound
         - inducible isoform not commonly found in most tissues               hematemesis,            maintain GFR & urine flow                                 -   enterohepatic recycling in dog
         - highly regulated – more enzyme produced in response to             diarrhea,            GI protectants                                                   (ibuprofen, naproxen, indomethacin,
            infection of cytokines                                            melena, abd          - Low dose exposures – AIOH or MgOH                              piroxicam, flunixin)
         PG – mediators of infection                                          pain, colic             antacids, kaolin-pectin demulcents (do                    -   metabolized to inactive forms
         - synthesized from arachadonic acid                               - PU/PD, oliguria,         not use bismuth subsalicylate-
         - initial step requires liberation of AA by phospholipase            anuria                  containing formulations)                                  Dogs, Cats, Ferrets, Horses
         - COX then catalyse converstions of AA  PG                       - Behavioral            - H2 blockers (famotidine, cimetidine,
         - Inhibit COX enzymes  inhibit prod of PG                           changes,                ranitidine) – reduces production of
                                                                              depression,             gastric acid & pepsin
         Toxicologic Mechanism:                                               seizures             - Proton pump inhibitor (omeprazole) –
         GI                                                                - Icterus                  inhibit transport of H+ ions into
         - Suppression of PG syn  ↓gastric defence mech                                              stomach, decreasing acid production
         - PG mediate gastric mucous & bicarb secreation, blood flow,      Lesions:                - PGE1 analogue (misoprostol) – direct
            epith cell turnover & repair, mucosal immunocyte fxn           - GI irritation,           action on parietal cells to inhibit
         - GI ulceration is due to inhibiton of PG responsible for            hyperemia,              gastric acid secretion
            inhibiting the secreation of Gastrin & HCL                        erosisons,           - Sucralfate (carafate) – binds to
         - NSAIDS  Topical irritants                                         ulcerations,            exudates at ulcer sites (in acidic
         - Epitheial damage due to accum of NSAIDS in cells (ion              edema,                  environ)
            trapped) & ability of NSAIDS to ↓ hydrophobicity of               perforation
            mucous layer in stomach                                           (most common
         - NSAIDS may impair gastric mucosal microcirc by                     in stomach)
            attracting neutrophils  form thrombi & obstruct               - Horses: right
            capillaries                                                       dorsal colitis
         Renal (analgesic nephropathy)                                     - Necrosis of
         - Animals that are vol depleted, have pre-existing renal dz,         tubular epith
            hypotensive or other nephrotoxic durgs  ↑risk                    cells, collecting
         - Chronic use but also high acute dose  ↑ risk                      ducts, loops of
         - Inhibition of renal PG that modulate renal blood flow             Henle (renal
            ↑vascular resistance, constriction of renal capillary beds,       papillary
            redistrubtion of blood away from medulla (**Papillary             necrosis)
         - Direct cytoxicity                                               ***Triad***
         Platelet                                                          - Ulcerations
         - Decreased platelet aggregation (aspirin)                        - Right Dorsal
         Hepatotoxicosis                                                      Colitis (horse)
         - Not common                                                      - Renal Papillary
         - Assoc w/ carprofen in Labs                                         necrosis
         - Following withdrawal form drug, supportive treat, &
            washout time, animal was able to tolerate drug
         -                                            -                                            -                                           -                -
Cholecalciferol    -   CALCITRIOL (1,25                          12-72 hrs                                     -   Decontaminate – emesis, repeated           -   Good w/        Sources
(Vit D3)               Dihydroxycholecalciferol) is most         - Vomit, diarrhea (+/- blood), anorexia,          AC/CT                                          prompt         - most common exposure for pets =
                       active form  binds to Vit D                 depression, PU/PD                          -   Obtain baseline Ca, P, BUN,                    decontam &        rotenticides
                       receptors greater than calcifediol (25-   - ↑ Phos (usu P goes up before Ca)                Creatinine (repeat daily for 4 days –          no soft        - dietary supplements
                       Hydroxycholecalciferol) &                 - ↑ Ca                                            hypercalcemia will develop by then if it       tissue         - plants - Solanum malacoxyon, Day
                       cholecalciferol                           Renal impairment                                  is going to)                                   mineralizati      booming jasmine (Cestrum
                                                                 - mineralization                              -   If normal after 4 days (96 hrs)  no           on                diurnum)
                   ↑ serum Ca                                    - ↑BUN, creatinine, isosthenuria                  further treat                              -   Poor w/        - Dovonex (calcipotriene = clacitriol
                   - ↑ intestinal absorb Ca                                                                                                                       mineralizati      analogue) – oint for psoriasis
                   - Stim osteoclastic resorption of Ca &        Diagnosis                                     Hypercalcemic                                      on
                      P from bone                                r/o causes of Hypercalcemia                   - IV Saline (Na competes w/ Ca for renal                          -   Rapidly absorbed via ingestion
                   - ↑ renal Ca reabsorption                     - PTH/PTHrp/Calcifediol (25-                    tubular reabsorption) avoid Ca fluids                           -   Metabolites highly lipophilic
                                                                     Hydroxycholecalciferol) – will not pick   - Furosemide (Ca wasting  ↑ renal                                -   Enterhepatic recirc
                   -   soft tissue mineralization = Ca X P           up Dovonex (calcitriol analogue)            calcium excretion) Avoid Thiazide                               -   Long half-life
                       >70                                       Postmortem – bile, kidney, urine for            diuretics (Ca sparing)                                          -   Converted to calcifediol
                   -   calcification  structural &              calcifediol                                   - Oral Prednisone (↓bone resorption of                            -   Metabolic activation in kidneys to
                       functional damage to kidneys, GIT,        - Renal Ca-P ratio elevated in EG               Ca, intestinal absorption of Ca, ↑renal                             calcitriol (active VitD) – plasma T ½
                       cardiac muscle, blood vessels, skel           (compared to cholecalciferol)               Ca excretion)                                                       3-5 D
                       muscle, ligaments                                                                       - Phosphate binders (aluminum                                     -   Further memtabolized to inactive
                                                                                                                 hydroxide - ↓dietary phosphorus                                     calitoic acid  elim in bile & feces
                   Lesions                                                                                       absorb)                                                         -   No relay toxicosis
                   Grossly                                                                                     - Low Ca, Low P Diet (↓Ca/P
                   - Mineralization of kidneys, gut, cardiac                                                     absorption)
                      & skel muscle, tendons, ligs.                                                            - Avoid sunlight
                   - Oral & gastric ulceration secondary to                                                    - Bisphosphonates (Pamidronate) –
                      azotemia                                                                                   inhibits osteoclase bone resorption,
                   Histo                                                                                         does not interfere w/ bone formation,
                   - Crystalline mineral deposits in tubular                                                     fluid load before to protect kidneys,
                      basement mem & bowman capsule                                                              espensive but work rapidly (24 hrs)
                   - Proteinaceous casts                                                                       - Calcitonin (inhibits osteoclast bone
                   - GI mucosal necrosis, sloughing,                                                             resorption) admin repeatedly,
                      hemorrhage, mineralization                                                                 ↓effectiveness if used w/
                   -                                             -                                             -                                              -                -
Soluble Oxalate-   Soluble Oxalates (Na & K salts of Oxalic      -   Hypocalcemia w/in 2-6 hrs                 - 1:3 ratio of dicalcium phosphate: NaCl       sources
Containing         Acid)                                         -   Dullness, rumen atony, bloat,               may bind soluble oxalates in gut             - Shamrock (Oxalis)
Plants             - water soluble                                   twitching, ataxia, teeth grinding,        - Not successful - treatments for              - Rhubarb
                   - rapidly absorbed from gut & rapidly             tetany, seizures                            hypocalcemia, acidosis, renal failure        - Dock (Rumex)
                      excreted                                   -   Bradycardia, slobbering, weakness,                                                       - Halogeton
                   - Oxalic acid complexes w/ serum Ca               incoordination, coma                      Prognosis – poor by time signs noticed         - Greasewood (Sarcobatus)
                       hypocalcemia                             -   Vomiting, depression, weight loss,                                                       - Lambsquarters (Chenopodium)
                   - Fatal renal tubular necrosis from               diarrhea, death                           Prevention
                      crystallization of excreted calcium        -   ↑BUN, creatinine                          - Feed high quality diet & limit exposure      Insoluble Oxalates = oxalate crystals (usu combined w/
                      oxalate in kidneys                                                                          to oxalate containing plants                Ca)
                   - most soluble oxalate-containing             Lesions                                                                                      - vegetative parts of the plant contain needle shaped
                      plants are OUTDOOR PLANTS                  - Ca oxalate crystals in tubular lumen,                                                         crystals arranged in bundles = raphides
                                                                    lumen distension, flattened degenerated                                                   - raphides are contained w/in specialized cells that have
                   -   Highest conc in rapidly growing plants.      tubular epith                                                                                thick, rigid walls (Idioblasts)
                       Leaves contain highest conc compared                                                                                                   - upon mechanical pressure to idioblast (mastication) 
                       to stems or seeds                         Diagnosis                                                                                       raphides expelled
                   -   Toxicosis depends on rate of              - Plant ID in gut                                                                            - raphides penetrate mucosal tissue  allow entry of other
                       consumption, amt of other feed            - Ca oxalate crystals in kidney                                                                 irritant substances (enzymes or oxalic acid)
                       consumes concurrently, total amt of       - Measure oxalate conc in forage & kidney                                                    - Insoluble oxalate containing plants cause primarily
                       oxalate consumed                                                                                                                          ORAL & GI irritation & are commonly
                   -                                                                                                                                             HOUSEPLANTS
Boric Acid &      -   unknown                                  -   most exposure in small animals         -   Symptomatic & supportive (NPO) for          -   Sources
Borates                                                            mild, self limiting vomiting                most                                            - Medical, household, industrial
                                                                                                           -   Fluid & elet if vomiting is severe or           - Most common = control prod fro
                                                               -   High Doses  renal & CNS effects            persists                                           roaches, ants, flies, fleas
                                                                                                                                                               - Borax (sodium borate) – applied to
                                                               -   dependent upon amt ingested, conc of                                                           carpets for fleas
                                                                   agent, age & general health of animal                                                       - Ant baits (sodium tetraborate)
                                                               -   High acute exposures or chronic
                                                                   exposures  multiple organ sys                                                              -   Readily absorbed through damaged
                                                                   involvement possible                                                                            skin
                                                                                                                                                               -   Rapid & complete absorption from
                                                                                                                                                               -   Excreted unchanged in kidneys

                                                                                                                                                               -   Ingestion, injection, enemas, topical
                                                                                                                                                                   exposure to damaged skin, lavage of
                                                                                                                                                                   body cavity  poisoning
                                                                                                                                                               -   Accidental admin to infants
                                                                                                                                                               -   Young & geriatric animals at greater
                  -                                            -                                           -                                               -   -
Grapes &          -   unknown                                  -   vomiting w/in few hours                 -   early & aggressive decontam – emesis,       -   -   DOGS
Raisens                                                        -   24 hrs: depression, anorexia                AC/Ct                                           -   any type
                  Lesions                                                                                  -   baseline BUN, Creatinine, Ca, P                 -   any breed
                  - renal prox tubular degeneration &          acute renal failure                             (recheck daily for 4 days)                      -   Not all ingestions result in renal
                     necrosis                                  - 24-36hrs: ↑BUN, ↑creatinine,              -   IV fluids – saline (2x maint) – 48 hrs              failure
                  - mineralized tubular debris                 - 36-72 hrs: lack of urine                  -   Monitor urine output
                  - regeneration (BM intact)                   - ↑Serum Ca (not usu assoc w/ ARF)          -   Promote dirureses (furosemide,
                                                                                                           -   Peritoneal or Hemodialysis
                  -                                            -                                           -                                               -   -
Pigweed           -   NITRATES & small amts of                 -   Depression, weakness, trembling,        -   symptomatic & supportive treatment for      -   -   found in ditches, fencerows,
Redroot Pigweed       SOLUBLE oxalates                             incoordination, recumbancy                  remia                                               cultivated soils, gardens, cattle lots,
(Amaranthus       -   NEPHROTOXICANT (unidentified)            -   Ventral edema, fluid distended          -   renal lesions not likely to be reversed            wate areas
retroflexus)      -   CATTLE & PIGS most common (also              abdomens                                    poor prog                                       -   lower stems red or red-streaked
                      sheep, goats, horses)                    -   ↑BUN, creatinine
                  -   Renal tubular nephrosis (w/out oxalate   -   hypocalcemia, hyperphosphatemia         Control
                      crystals)                                                                            - keep stock well fed
                                                               Diagnosis                                   - avoid exposure to pigweed – mowing,
                  Lesions                                      - history, lesions, evidence of ingestion     herbicides
                  - PIGS & CATTLE: Ascites,
                     ****PERIRENAL EDEMA
                  - Kidneys swollen, pale
                  - Proximal & distal tubular necrosis
                  -                                            -                                           -                                               -   -
Oak poisoning      -   GALLOTANINS                                - Acorn husks in feces                         -   Symptomatic & supportive                   -   Poor            -   buds, twigs, leaves, acorns
Acorn poisoning    -   Renal lesions not reproduced by            - ↑BUN & creatinine                                                                           -   If survive      -   immature leaves in spring &
(Quercus sp)           experimental admin of tannic acid          Cattle                                         Control                                            initial acute       freshly fallen acorns in fall = most
                   -   TANNIC ACID responsible for GI &           - Early: Constipation, brown-colored           - Feed animals well                                toxic phase         common
                       liver lesions                                urine                                        - Ca hydroxide as a feed supplement                 may
                                                                  - Followed by: anorexia, depression,             ↓toxicity by binding to Tannic acid              make            -   CATTLE, occasional horse
                   Lesions                                          rumen atony, diarrhea                                                                           complete        -   Lack of forage  ingestion more
                   Cattle                                         Horse                                                                                             recovery            likely
                   - **Perirenal Edema, retroperitoneal           - Colic, ↓peristalsis, depression,
                      edema, ascites, hydrothorax                   constipation
                   - kidneys pale & swollen w/ petechial          - Tenesmus, hemorrhagic diarrhea,
                      hemorrhages                                   hemoglobiuria, hematuria, icterus
                   - ulcerations & hemorrhage anywhere on
                      GIT                                         Diagnosis
                   Horse                                          - Pyrogallol (metabolite of tannic acid)
                   - hemorrhagic enteritis & severe edema            detected in serum & urine of cattle early
                      of mesentery, cecum, large intestine           in synd (before clin signs present)
                   -                                              -                                              -                                              -                   -
Lillies            - Water soluble                                - Initial vomiting, salivation, lethargy,      -   early & aggressive decontam – emesis,      -   Poor w/out      sources
(Lilium sp         - Toxic principle not ID                          anorexia (2-6 hrs)                              AC/CT                                          treat           - Easter lilly
Hemerocallis sp)                                                  - ↑BUN, creatinine, K, Phosphorus (24-         -   IV fluids (2-3x maint) 24-48 hrs           -   Good w/         - Tiger lily
                   -   Necrosis of renal proximal tubular epith      72 hrs)                                     -   Peritoneal or hemodialysis – keep              immed           - Japanese Show lily
                       cells  sloughing into lumen              - oliguria, anuria                                 patient alive until tubules repair             aggressive      - Day lilies (Hemerocallies)
                       plugging of tubular lumen                  - **creatinine often disproportionately            themselves                                     treat & no      - Hybrids
                   -   Dehydration which exacerbates the             elevated compared to BUN                                                                       clin signs      - NOT: Peace lily (oxalates), Calla
                       renal damage & promotes anuria             - epithelial casts & glucose in urine by       Control                                                               lily (oxalates) Lily of the valley
                                                                     18 hrs                                      - Prevent exposures by restricting access to                          (cardio)
                   Lesions                                                                                         plants
                   - Swollen kidneys w/ perirenal edema           Diagnosis                                                                                                         -   ONLY CATS
                   - Diffuse acute renal tubular necrosis         - no test (toxic princip not known)                                                                               -   All parts of plant are toxic
                      (usu proximal tubules, occas distal)        - history, proximity to lilies                                                                                    -   Small amt can cause synd
                   - Granular & hyaline casts
                   - **BM intact  tubular regeneration
                      w/ supportive measures
                   -                                              -                                              -                                              -                   -
Ochratoxin         - targets renal prox tubule                    High doses: GI                                 -   AC may be effective for high dose acute    -                   -   Sources
A, B & C           - binds strongly to proteins                   - Gastroenteritis, diarrhea, emesis,               (not practical)                                                -   Produced by molds Aspergillus &
                   - interferes w/ syn of tRNA & mRNA                tenesmus, depression, anorexia,             -   Symptomatic & supportive for renal                                 Penicillum
Porcine            - interferes w/ prot syn                          dehydration                                     insufficiency                                                  -   Production of specific mycotoxins
mycotoxin          - disrupts carb metabolism                     Low doses (chronic exposure from field):                                                                              depends on moisture & temp
nephropathy        - ↑generation of free radicals                 urinary dysfunctions                                                                                              -   Barley, rye, wheat, corn contaminated
                                                                  - PU/PD, ↓produciton, ↑BUN, creatinine                                                                            -   Stable toxins unaffected by storage
Balkan endemic     Lesions
nephropathy        Gross                                          Diagnosis                                                                                                         -   Well absorbed from gut
                   - Pale enlarged kidneys w/ rough irreg         - Feed, liver, kidney, less commonly milk,                                                                        -   Protein bound in blood to small
                      surface                                        plasma, urine                                                                                                      molec weight protein fractions
                   - Cut surf: pale cortical streaking &                                                                                                                            -   Passes through glomerular mem,
                      small cystic areas typ of fibroplasias                                                                                                                            reabsorption in prox & distal tubules
                   Microscopic                                                                                                                                                      -   Enterohepatic recirc
                   - Renal tubular swelling, loss of epith                                                                                                                          -   C & D contribute to prolonging T ½
                      brush border, degen of mito & ER,                                                                                                                             -   Toxicity influenced by species, age,
                      necrosis                                                                                                                                                          diet, sex, ROA, form of toxin
                   - interstitial fibrosis & dilated tubules                                                                                                                        -   SWINE
                      w/ flattened renal tubular epith
                      characteristic of chronic lesions
                   - thick BM & sclerosis of glomeruli
TERATOGENS, ABORTIFACIENTS, INFERTILITY                                                                      -                                               -   -
                  -                                           -                                              -                                               -   -
False hellebore   -   5 groups of AZASTEROIDS                 -   Affected lambs born w/ varying degrees     Control                                         -   -   western US
(Veratrum             (nitrogenous steroidal alkaloids):          of facial deformity                        - Keep sheep off of pastures continuing             -   moist sites & higher elevations
californicum)         veratranine, cevanine, jervanine,       -   Cycopia, protruding & twisted madable,       plants, esp during first trimester
                      solanidanine, cholestane                    shortened upper jaw, proboscis-like        - Delay breeding season until after the first       -   leaves & stems are acrid & burning
White hellebore   -   JERVANINE (only teratogenic) –              structure located above eye (“monkey         killing frost                                     -   SHEEP most susceptible
Corn lily             cyclopamine, cycoposine, jervine,           face”)                                                                                         -   Cattle, goats, llamas also suscep
Skunk cabbage         veratrobasine                           -   Prolonged gestation possible due to lack                                                       -   Alkaloid leaves highest in eaves
                  -   Cyclopamine  fetal deformities             of pituitary                                                                                       June-July (then decline)
                  -   Jervanine parent cmpds act directly     -   Most deformed lambs born dead or die                                                           -   Pregnant ewes consume on 14th
                      upon fetus (no metabolic activation)        shortly after birth                                                                                DAY GESTATION 
                  -   All azasteroids produce hypotension                                                                                                            characteristic facial deformity &
                      & neuro effects (minor compared to      Diagnosis                                                                                              cyclopia
                      repro effects)                          - Characteristic lesions & History of                                                              \
                                                                 exposure                                                                                        -   D12-14  cyclopia
                  -   Mech unknown                                                                                                                               -   D12-34  motor nerve paralysis
                  -   May act upon stem cells during early                                                                                                       -   D24-30  cleft palate
                      mesenchymal differentiateion into                                                                                                          -   D25-36  hypoplasia of
                      cartilage                                                                                                                                      metacarpals, metatarsals
                  -   Neurohumoral effects through
                      inhibition of ACh
Tobacco           -   ANABASINE                               -   Arthrogryposis, scoliosis, kyphosis,       Control                                         -   -   Feed discarded tobascco to preg
(Nicotiana sp)    -   Piperidine alkaloids = basic cmpds          torticollis, cleft palate                  - Avoid plants during critical per of                   SOWS  Skeletal malformations &
                      that are derivatives of piperidine      -   Normal bone development – lesions are        gestation                                             cleft palate
                  -   Neuromuscular blockers that prevent         contracture-type assoc w/ lack of fetal    - Control weeks w/ broadleaf herbicide              -   Teratogenic to PIGS, LAMBS,
                      normal fetal movement during                movement in utero                                                                                  CALVES
                      critical stages of gestation                                                                                                               -
Poison Hemlock    -   Piperidine alkaloids                    -   Arthrogryposis, scoliosis, kyphosis,       Control                                         -   -   CALVES, PIG, LAMB
(Conium           -   CONINE, CONICEINE, conhydrine               torticollis, cleft palate                  - Avoid plants during critical per of
maculatrum)       -   Neuromuscular blocers that prevent      -   Normal bone development – lesions are        gestation
                      dnormal fetal movement during               contracture-type assoc w/ lack of fetal    - Control weeks w/ broadleaf herbicide
                      critical stages of gestation                movement in utero
Lupine            -   Piperidine alkaoids: ammodendrine,      -   Arthrogryposis, scoliosis, kyphosis,       Control                                         -   -
(Lupinus sp)          hystrine                                    torticollis, cleft palate                  - Avoid plants during critical per of
                  -   Quinolizidine alkaloid: anayrine        -   Normal bone development – lesions are        gestation
“Crooked Calf     -   Reduced fetal movement during               contracture-type assoc w/ lack of fetal    - Control weeks w/ broadleaf herbicide
Disease”              critical stages of gestation                movement in utero
Locoweeds         -   SWAINSONINE – readily cross             -   LAMBS & CALVES – born weak &               Control                                         -   -
(Astragalus sp)       placenta, excreted in milk                  often diet at a few days of age            - Avoid plants during critical per of
                  -   Inhibits action of mannosidases        -   Others smaller than normal or w/ head &      gestation
                      cell accum oligosaccharides                limb deformities                           - Control weeks w/ herbicide
                      disrupt normal structure of             -   Crooked legs likely due to ↓fetal
                      glycoprot  generalized lysosomal           movement
                      storage dz                              -   Exposure of preg MARE early in
                  -   Placental vulnerable to locoweeds at        gestation  foals w/ corked legs due to
                      any stage  Esp FIRST 90 DAYS of            deformity of bones of fetlock
                      preg  normal placentation affected
                       fetal resoprtion, abortion,
                      infertility, hydrops allantois,
                      SQedema in fetus, fetal deformities
Mercury           -   ORGANIC mecurials, esp                  -   KiTTENS - Cerebellar hypoplasia if born    Control                                         -   -
                      METHYLMERCURY                               to queens exposed to during gestation      - Awareness & prevention of exposure
                  -   Interfere w/ metabolic activity &       -   Selective damage to granular cells of        during preg
                      prevent synthesis of essential prot        cerebellum in ALL species
                      cell degeneration & necrosis            -   Can mimic panleukopenia in CATS
Fescue              -   FUNGAL ENDOPHYTE                        -   ***4 major syndromes                                       - remove from source of            -   mild            -   tall fescue grass from
(Festuca                Neotyphodium coenophilaum -                                                                              endophyte-infected fescue (esp       symptoms            pastures or in hay
arundinacea)            fungus grows in intercellular spaces    Fescue Foot                                                      last 30-90 days of gest in            resolve       -   lower Midwest & upper SE
                        of leaves, stems, seeds                 - similar to ergotism in cattle & sheep (Dry Gangrene)           mares)                               w/ minimal          US, “south of I-70 Illinois)
Fescue toxicoisis                                               - 1 or more weeks following intro to tall fescue hay or        - provide nutrient rich diet –         treat           -   symbioitic relationship btwn
Fescue food         2 classes of ERGOT ALKALOIDS                   pasture                                                       fossibble role for ergot         -   tissue &            grass & endophyte  grass
Summer slump        - Ergoline alkaloids – lysergic acid,       - most common in cooler weather (fall/winter)                    alkaloid binders                     necrosis &          w/ endophyte has higher
Summer synd             lysergol, ergonovine                    - extremities affected – esp hind limbs, tips of tail & ears   Cattle                                 shoughing           disease & insect resistance
Fat necrosis        - Ergopeptine alkaloids –                   - swelling & reddening of coronary band, knuckling of          - D2 recetpor antagonists              (fescue
Lipomatosis             ERGOVALINE, ergosine,                      pastern, shifting of weight from one hind limb to the         (metoclopramide, pinquidone          foot) or abd    -   CATTLE, SHEEP, HORSES
                        ertogamine, cergocristine,                 other  can progress to ischemic necrosis & sloughing       - Alpha adrenergic antagonist          obstruct (fat   -   Mares: PRL & gestation
                        ergocomine                                 of hooves                                                     (prazosin)                           necrosis)          abnormalities unique to
                                                                - often distint line of demarcation btwn necrotic & viable     - Serotonin receptor blocker           not likely to   -   Cattle/Ruminants: Fescue
                    Vasoconstriction                               skin                                                          (phenoxybenzamine)                   recover             foot, summer slump, fat
                    - Inhibition of D1 dopamine                 - osteomyelitic changes consistent w/ septic arthritis         Mares                                  (euthanasia)        necrosis
                      receptors & partial agonism of                                                                           - Domperidone to treat             -   early           -   Environmental factors affect
                      alpha adrenergic & serotonin              Summer Slump                                                     agalactia, Rapid ↑circ levels        recognition         levels of ergot alkaloids in
                      receptors                                 - most common & economically sig                                 of progestin & PRL, Does not         & treat in          endophyte infectec fescue:
                    - Impaired circ to extremities, abd &       - ↓ cutaneous heat transfer & endocrine imbalances              cross BBB (neuro SE low)             late gest           seasonal variations, stages of
                      pelvic fat stores, placenta                 impaired thermoreg                                                                                  mares              plant growth, fertilization,
                    - Hyperthermia, dry gangrene,               - ↓feed intake, weight gain, growth rate, ↓milk prod,          Control                                good prog           pasture management
                      necrotic fat, altered placental fxn         delayed shedding of haircoat, imnnosuppress, ↓repro fxn      - Strategic avoidance of                               -   High temp & humidits, lack
                      (& abortion)                              - lethargy, diarrhea, hyperthermia, tachypnea, seek shade        endophyte infected fescue                                of water, inadeq nutrition –
                                                                  or stand in H2O                                                pastures – during extreme heat                           may predispose animals
                    Decreased Prolactin Secretion                                                                                or cold for ruminatns, 30-90
                    - Stimulation of D2 dopamine                Fat necrosis (lipomatosis)                                       dyas prior to parturition for
                      receptors  ↓PRL secretion                - presence of necrotic fat in abd & pelvic spaces                mares
                    - PRL required for lactation &              - often asymptomatic – requires grazing of heavily             - Replace w/ endophyte free
                      parturition                                  fertilized endophyte infected fescue for several seasons      fescue
                    - Result: hypo/-agalactia, delayed          - masses of necrotic fat detected – rectal palp                - Dilution of fescue parturew w/
                      parturition                               - necrotic fat masses may cause obstruction  bloating,          legumes (clovers)
                                                                   colonic constriction, dystocia, nephrosis, uremia           - Ammoniation of hay my
                    Clin Path                                   - Grossly: hard, caseous, yellow or chalky white, nodues         decrease effects of fescue in
                    - Chronically exposed cattle: ↑RBCx,           or masses of adipose tissue                                   cattle
                       ↓cholesterol, globulin, TP, ↓ALT &       - Histo: coag necrosis of adipocytes & occasional foci of
                       ALP, ↑Bili & Creatinine, ↓serum             macrophages & saponification
                       copper, ↓serum PRL
                    - Foaling Mares: reflection of trauma       Equine fescue toxicosis (agalactia-dystocia synd
                       assoc w/ dystocia – inflam, infection,   - Late gestation & early postpartum
                       septicemia, endotoxemia, stress          - Agalactia, prolonged gest, abortion, dystocial, fetal
                    - Newborn Foals: reflection of dystocia       asphyxia, weakness, dysmaturity, mortality, premature
                       or FPT - ↓blood IgG                        placental separation, thickening & edema of featl mem,
                    - Late gestation mares: ↓plasma or            retained placenta
                       serum PRL, progestins, relaxin           - Absence or ↓ in normal prepartum physiological
                                                                  development in mares – udder develop & accum of
                    Diagnosis:                                    colostrum at teat orifices (waxing)
                    - Detect N. coenophialum in plant           - ↑fetal size  dystoia & life threating complications
                    - Determine conc ergovaline in forage         (maternal tissue trauma, metritis, septicemia,
                       or hay – must correlate w/ direct          endotoxemia, laminitis, FPT, neonatal septicemia
                       evidence of consumption                  - foals are overmature w/ overgrowh hooves, irreg dental
                    - Analysis of biological tissues for the      eruption ↓muscle mass & flexor tendon laxity
                       ergot alkaloids or their metabolites –   - fetal mem – grossly thickened, edematous, ↑cellularity &
                       ELISA for urinary excretion                CT
NitrAte (NO3) /     -   NITRITE = toxic cmpd                 -   As early as 1-4 hrs & assoc w/ tissue oxygen     -   Minimize handling & stress                   -   Difficult to     -   Plants stressed or damaged by
NitrIte (NO2)           (monogastrics)                           deprivation                                      -   Methylene Blue as a 1% soln in                   ascertain            drought, frost, herbicides, hail
                    -   NITRATE = toxic (RUMINANTS)          -   Weakness, exercise intol, dyspnea, ataxia            physiologic saline given slowly IV,          -   If cattle live   -   ↓capacity for photosynthesisi
Methemoglobine                                               -   Tacchycarddia, depression, tremors, muddy            repeat as needed. Wide margin of safety          more than        -   roots & stems continue to supply
mia                 -   Normal: NitrAte  NitrIte in             or cyanotic mm, collapse, terminal                   in cattle, NOT safe in cats (oxidizing           24h                 NitrAtes to upper protions of plant
                        rumen, then NitrIte  ammonia            convulsions                                          agent)                                           likely to        -   ↓photosyn  ↓incorportation of
                        (NH3) for incorporation into         -   Animals at rest may not exhibit signs until                                                           survivie             NitrAtes into other plant
                        microbial proteins                       forced to move                                   Control                                          -   Affected             constituents  nitrate accum
                    -   NitrAte  NitrIte is a rapid rxn     -   Death by 6-24 hrs                                - Monitor nitrate conc in forages fed to             fetus may        -   New leaf growth & concomitant
                    -   Rate limiting step = NitrIte  NH3   -   Abortion from sublethal nitrate intoxication       cattle, esp preg cattle                            not abort for        photosyn will eventually utilize
                                                                 in the dam, usu 3-7 days after exposure.         - Allow for adaptation of cattle to high             3-7 days             nitrAtes & ↓ conc
                    -   High nitrAte consumption  excess        Aborted fetuses may exhibit                        nitrate forage, dilute w/ low nitrate forage                        -   NitrAte not affected by drying
                        NitrIte absorbed into bloodstream        methemoglobinemia or elevated ocular fluid       - If forage found to be high in nitrates,                             -   \
                    -   NitrIte oxidizes Ferrous heme iron       nitrate conc                                       delay harvesting until conditions allow                             -   Nitrate based fertilizers
                        (Fe2+) to Ferric heme iron (Fe3+)                                                           for nitrate levels in stalks to decrease,                           -   Water containg Nitrate
                         methemoglobin                      Diagnosis                                              raise harvesting cutter bar  leaving                               -   Improperly mixed feed
                    -   Normal hemoglobin oxygenation       - Clin signs – brown, muddy, chocolate colored         high nitrate stalks in field
                        no change in oxidation state of         blood & mm                                        - Harvest 3-4 days after rainfall                                     -   Rumen metab of NitrAte  NitrIte
                        heme iron (stays Fe2+)               - Finding excess NitrAte in plasma, serum,           - Ensiling can reduce nitrate conc – test                             -   Rapid absorb nitrAte & nitrIte from
                    -   Change to Fe3+  Formation of           blood, forages, urine, ocular fluid               - Rumen inoculation w/ nitrate-protective                                 GIT
                        methemoglobin  cannot carry O2      - Methemoglobin testing su not practical (rapid        strains of propionibacteria                                         -   Peak methemoglobinemia by 3 hrs
                    -   Some methemoglobin formation            post-mortem degredation)                                                                                                -   Monogastrics excrete nitrates into
                        naturally occurs in body, but is                                                                                                                                    urine
                        reconverted to Hb by enzyme in                                                                                                                                  -   Can cross placenta to affect fetus
                        RBCs. Oxidants exceed the                                                                                                                                           (↑ocular NitrAte conc, fetal
                        capacity for this reconversion                                                                                                                                      methemoglobinemia)

                    Lesions                                                                                                                                                             -   Plant stress that affects nitrate use:
                    - Brown or chocolate colored blood &                                                                                                                                    excess or restrictedmoisure, high
                       brownish cast to all tissues                                                                                                                                         temps, unusually cool & clody
                    - Methemoglobinemia (unstable post-                                                                                                                                     weather, leaf-damaging hail or
                       mortem)                                                                                                                                                              frost, herbicide application, large
                                                                                                                                                                                            amts of nitrates available for plant
                                                                                                                                                                                            uptake, plant species, plant part,
                                                                                                                                                                                            post-harvesting storage
                    -                                        -                                                    -                                                -                    -
Isocupressic Acid   -   ISOCUPRESSIC ACID = toxic            -   abortion from 2 days – 2 weeks after ingestion   -   none for impending abortion                  -                    -   Ponderosa pine, Lodgepole pine,
                        principle                                – depends on gestational age, amt consumed,      -   remove retained placena & treat for                                   Common Juniper, Montery cypress
Pine Needle         -   exact mech unknown                       conc of isocupressic acid present                    metritis, septicemia                                              -   Found in needles, bark, new growth
Abortion            -   may cause reduction in uterine       -   cattle exhibit premature udder development &                                                                               tips. Needles most likely consumed,
                        blood flow to fetus                      milk prod, vulvar sewlling, mucoid or            Control                                                                   found in both fresh or dry
Pinus sp            -   may be due to activation of α2-          hemorrhagic vaginal discharge, retained fetal    - deny preg cattle access to pine needles
Juniperus sp            adrenergic receptors  ↓in               mem                                                during last trimester of preg                                       -   COWS in LAST 3 MOS preg at
                        nutrients & O2 to fetus  stim       -   premature calves generally small & weak, may                                                                               greatest risk (3rd trimester 
                        release of fetal cortisol  direct       not survive                                                                                                                abortion)
                        stim for parturition in cows                                                                                                                                    -   Hungry cattle more likely to consume
                                                             - clin signs & Hx
                                                             - no specific tests
                    -                                        -                                                    -                                                -                    -
Zearalenone      -   acts as weak estrogen                        Prepubertal gilts most sensitive                  -   Remove from feed source        -   Good         -   Mycotoxin produced by Fusarium sp
                 -   binds receptors for Estradiol-17β            - D7-10 post mating = most CRITICAL PER,                                             -   Signs usu    -   Usu in corn. (also wheat, sorghum,
                                                                      Implantation failure – females appear        Control                                reversible       barley, oats, sesame seed)
                                                                     infertile, ↓#s CL, ovarial atrophy             - Adequate drying of grain                          -   Zeanol (Ralgro growth promotent)
                                                                  - Pseudopregnancy, anesterus, edematous vulva     - Dilute w/ clean feed, or feed                     -   Environmentally stable\
                                                                     (vulvoganitis), vaginal & rectal prolapses       contam feed to less sensitive
                                                                  - Uterus: enlarged, tortuous, edematous             species (feeder cattle)                           -   Rapid absorb from GIT
                                                                  - Enlargement of mammary gland                    - Monitor for concurrent contam                     -   Metabolized & conjugated to
                                                                                                                      w/ DON (Vomitoxin)                                    glucuronide in liver
                                                                  Effects on offspring In Utero                                                                         -   Enterohepatic recycling
                                                                  - Blastocysts deteriorate, fetal resorption,
                                                                     mummies, reduced litter size, weak or                                                              SWINE most sensitive
                                                                     stillborn pigs, abortions                                                                          - Females: infertility, failure of
                                                                                                                                                                           implantation, EED
                                                                  Effects on Male Swine                                                                                 - Young boars: ↓testes weight,
                                                                  - Young boars  atrophy of testes                                                                        spermatogenesis, libido
                                                                  - Castrated males  mammary gland                                                                     - Mature boars unaffected
                                                                     enlargement                                                                                        Cattle more tolerant, but still sensitive to
                                                                                                                                                                        high doses
                                                                  Diagnosis                                                                                             POULTRY Resistant
                                                                  - Detest zearalenone in feed
                                                                  - Tissue analysis unrewarding
                 -                                                -                                                 -                                  -                -
Phytoestrogens   - White Clover                                   -                                                 -                                  -                -
                 - Subterranean clover
                 - Alfalfa
                 -                                                -                                                 -                                  -                -
Gossypol         Reproductive                                     Sows                                              -   Remove from feed source        -                -   yellow polyphenolic pigment found
                 - Rats: Suppress P4 & E2 during                  - Reduced conception rates, abortions, ↓litter    -   Dilute w. clean feed                                in glands of cottonseed (Gossypium
                   implantation                                     size                                                                                                    sp)
                 - Heifers: affect follicular development,        Male ruminants                                    control                                             -   amt of gossypol depends on growing
                   embryo recovery & production, CL fxn           - ↓sperm motility & sperm production              - Test cottonseed                                       cond & environ factors
                                                                  - damage to spermatogenic epith & ↓germinal       - Restrict gossypol in ration of                    -   processing method alters toxicity –
                 Cardiotoxic                                        cell layers                                        breeding animals                                     heating ↑binding of free gossypol 
                 - Affect movement of K+ across cell mem                                                                                                                   less toxic
                    hypokalemia                                   -   sudden death
                 - Heart sensitive  gradual destruction of       -   CHF w/ resultant chronic labored breathing,                                                       -   gossypol is bound to proteins in
                    cardiac muscle                                    exercise intol, fluid accum – “thumping”                                                              rumen
                 - Potassium supplementation may not correct      -   Infertility, abortions                                                                            -   MONOGASTRICS = most sensitive
                    gossypol-induced hypokalemia                                                                                                                             more susceptible b/c lack of
                 - Potassium disturbances may account for         Diagnosis                                                                                                 Protein binding  free gossypol
                    sudden death                                  - Analysis of feed                                                                                        absorbed
                 - Gradual heart failure may account for edema
                    & ascites

                 - No lesions may be detected
                 - Fluid accum due to CHF fluid in thoracic &
                    peritoneal cavities
                 - Pale, swollen, friable nutmeg livers
                 - Congestion of kidneys, spleen, pale muscles,
                 - heat may be enlarged & flabby, cardiac
                    muscle streaked, pale, mottled
                 - histo: myocardial degen, centrilobar liver
                    necrosis, pulm edema
PERIPHERAL CIRCULATION                                       -                                                       -                                             -                  -
                    -                                        -                                                       -                                             -                  -
Pit Vipers          -   multi components to venom both       -  Immediate, intense pain at bite site                 -  Do NOT use: cold packs, ice,               -   Good w/        ID
                        enzymatic & non-enzymatic - conc     -  Marked regional swelling (↑vasc perm)                   tourniquets, incision & suction,               early          - elliptical pupils
Crotalus –              varies from one envenomation to      -  Discoloration of skin w/ echymosis &                    electroshock, alcohol, DMSO topically,         recognition    - bilat heat sensing “pits” btwn eye &
rattlesnakes            another                                 petechiation (if coag factors affected)                 surgical debridement EARLY in                  & treat           nostril
Sistrurus – pygmy   -   Hyaluronidase (“spreading factor”)   - Bite site may be difficult to find (swelling &           course of synd                             -   Guarded to     - single row csubcaudal scales distal to
rattlesnakes            – cleaves hyaluronic acid in            hair) – clip hair, single or multiple                - Keep calm, maintain bitten extremity            poor w/           anal plate
Agkistrodon –           collagen  allows for rapid             punctures                                               below heart level, & transport to vet          delayed        - triangular shape head
water                   penetration of other venom           Severity of envenomation cannot be judged by            - Temp, RR, pulse, BP – monitor hourly            treat or       - retractable front fangs
moccasiaons,            components                           local tissue response                                   - Circumferential measurements above,             signif local   - snake can control amt of vvenom it
copperheads         -   Myotoxins – destroy muscle cells     - Seve systemic manifestations can occur w/                beow, & at bite site to monitor regional       & systemic        injects, “dry bites” = no venom
                    -   Phospholipase A – causes rupture        only mild local response                                swelling & progression                         rxns              injected
                        of myofibrils                        - Systemic signs more severe w/ rattlesnakes >          - Severity score sys to monitor severity                         - keratin rattle at caudal end of tails
                    -   Hemorrhagic toxins – both               water moccasins > copperheads least                     of snakebite, progression & response                          Sources
                        hypercoagulation & hypocoag          - Some species w/ only neurotoxins – so may                to treatment                                                  - all states ex HI, Maine, Alaska
                    -   Myocardial depressant factors           only inflict puncture wounds, but not                - IV crystalloid fluid therapy – prevent                            (mostly SE US)
                    -   Kallikrein-like activity &              produce severe neurologic deficity                      3rd spacing of fluids & hypovolemic                           - copperhead venom less potent than
                        metalloproteinase – marked local     Location of bite important                                 crisis                                                           rattlesnake
                        pain, tissue necrosis, systemic      - Head – possible obstruction to nares (esp             - Broad spec Abx                                                 - bites more common in hot summer –
                        hypotension                             horse), pharynx, tongue                              - Corticosterids controversial –                                    snakes more active & venom yields
                    -   Neurotoxin                           - Limbs – usu front legs                                   generally not rec                                                increased
                                                                                                                     IV antivenin:                                                    Toxicity
                    3 venom types                            -   Onset of significant signs may be delayed           - Avtivenin (Crotalidae) polyvalent –                            - snake: species, size, time of year,
                    - Diamondback rattlesnake –                  several hours – need to monitor for 12 hrs             equine origin – possible allergic rxns                           attitude, age, time since last bite
                       marked tissue destruction,                or more                                             - CroFab - ↓risk anaphylaxis                                     - victim: species, size, bite site, time
                       coagulopathy, hypotension             -   Cardiac arrythmias, tachycardia, shallow            - If anaphylaxis occurs, discontinue                                from btie to med care, amt of physical
                    - Mojave A rattlesnake – severe              resp, muscle fasciculations, hemolytic                 infusion, admin diphenydramine,                                  act since bite, preexisting med cond,
                       neurotoxicosis w/out tissue               anemia, hemorrhage, shock, renal failure               continue infusion at slower rate, keep                           medications
                       destruction or coag defects           -   Major cause of death  cardio collapse                 epi on hand
                    - INtergrade venoms contain both             resulting from hypovolemic shock                    - Delayed serum sickness also possible 7-
                       neurotoxins & cause tissue                                                                       10D later
                       destruction & coag defects            Clin path                                               - One vial sufficient for dogs
                                                             - Baseline CBC & serum chem – repeat 6,12,24            Efficacy of antivenin is best w/ early
                    Lesions                                     hrs                                                  admin
                    - TISSUE NECROSIS & sloughing            - Coag parameters: APTT, PT, fibrinogen,                Cannot correct tissue damage, but can
                       in region of bite site                   fibrin split products, platelet counts – baseline,   prevent it
                                                                6, 12, 24 hrs
                                                             - UA – monitor hematuria or rhabddomyolysis
                                                                6, 12

                                                             - Examine non-EDTA blood smear or 1 drop of
                                                                blood mixed w/ a drop of saline for
                                                                echinocytosis (w/in 12 hrs)
                                                             - Negative test does not rule out envenomation
                    -                                        -                                                       -                                             -                  -
Coral Snakes        -   multiple neurotoxic fractions          Cats                                                 -   Transport to vet                          -   -   Arizona, NM, Texas, SE US
                        combine to induce non-                 - Ascending, flaccid paralysis, loss of spinal       -   Draw beseline blood – CBC & chem.             -   Shy, reclusive, non-aggressive w/
Micururoides sp         depolarizing postsynaptic                reflexes in all limbs                              -   Monitor 24 hrs (onset of signs delayed)           low venom potency
Micrurus sp             neuromuscular blockade                 - CNS depression                                     -   Provide resp support if needed                -   Small heads, round pupils, primitive
                    -    manifested as vasomotor              - ↓BP, resp depress                                  -   Broad spec Abx                                    & inefficient venom delivery
                        instability, muscle paralysis, CNS     - anisocoria, hypothermia, myoglobinuria             -   May take Months for neuro signs to                apparatus
                        depression                             Dogs                                                     resolve                                       -   Fixed front fangs
                    -   enzymatic fraction can cause local     - CNS depression                                                                                       -   Envenomation requires chewing
                        tissue damage, hemolytic anemia,       - ↓spinal reflexes in all limbs                      Antivenin
                        hemoglobinuria, myoglobinuria          - resp depression, ↓BP, ventricular                  - Effective against all N. American coral         -   Neurotoxin – onset delayed 12 hrs or
                    -   vasodilation & ↓BP                       tachycardia                                          snakes except Sonoran Coral                         more
                                                               - vomiting, profuse salivation                       - Must admin eaerly for max                       -   Prolonged duration of synd – may
                                                               - hemolysis, hmoglobinuria, anemia                     effectiveness                                       take up to 14 D to clear body
                                                                                                                    - Monitor for allergic rxn (equine prot)          -   Severity related to size of victim &
                                                               -   cause of death is resp collapse                                                                        size of snake & motivation of snake
                                                               -   possible aspiration pneumonia due to
                                                                   dysfunctional swallowing

                                                               Clin Path
                                                               - elevations in Fibrinogen or CK
                                                               - Dogs – intravasc hemolysis, anemia,
                                                                  hematuria, burring & spherocytosis in red cells
                                                               - Cats – rhabdomyolysis - ↑myoglobin & ALP
                    -                                          -                                                    -                                             -   -
Recluse Spiders     necrotic arachnidism                       local (most common) = Dermal Necrosis                -   most cases do not require treat           -   -   sourthern half US
                    - spiders hibernate in winter - most       - w/in hours to a few days post-bite                 -   clean wound                                   -   violin shaped mark on dorsum of
Brown spider           bites between march & oct               - initially, cental blister w/ surrounding           -   brod spec Abx (clavamox – augmentin)              cephalothorax (carapace) – much
Fiddleback spider   - venom is complex mixture of                 edema & erythema                                  -   no specivic antidote                              darker than surrounding areas
Violin spider          enzymes                                 - progress to darkened center & development          -   Dapsone – controversial – may inhibit         -   long, think legs compared to body,
                                                                  of vesicle (bulls eye lesion)                         influx of neutrophils to site of bite             2nd pari of legs longer tan
Loxosceles sp       -   heparin sulfate proteoglycian &        - central area necrotic                                  (admin w/in 36 hrs of bite)  may                 remaining legs
                        laminin enactin  degradation of       - slow, progressive wound that is slow to heal           produce methemoglobinemia                     -   relusive, commonly found in
                        basement mem components                                                                     -   Symptomatic & supportive                          corners, closets, attics
                    -   hyaluronidase, lipase, alk             systemic (not common)                                -   Allow wound to granulate in – may             -   envenomation occurs when spider
                        phosphatase, esterases, proteases      - hemolysis, nausea, vomiting, fever,                    take weeks                                        disturbed or threatened
                    -   Fangs may introduce Clostridial orgs      generalized malaise                                                                                 -   **3 pairs of eyes in semi-circle
                        into wound                                                                                                                                        (most other spiders have 8 eyes) =
                                                               Clin path                                                                                                  best way to ID
                    sphingomyelinase  dermal necrosis         - coombs neg hemolytic anemia (systemic
                    - disruption of cell mem                     form)                                                                                               -   all mammals susceptible
                       microvascular damage & platelet
                    - chemotactic factor for recruitment of
                       inflam cells to wound
                    - influx of neutorphils & platelet
                       aggregation results in intravascular
                       coag in caps surrounding wound 
                       dermal necrosis

                    -                                          -                                                    -                                             -   -
Gangrenous        -   ERGO PEPTINE ALKALOIDS &               -   Similar to fescue foot                            -   Remove animal from source            -   -  some clinical signs indistinguishable
ergotism              ergoline alkaloids                     -   Extremities affected, esp hindlimbs, tail tips,   -   Mild signs are reversible                   from fescue (fescue foot)
                  -   Vasoconstriction assoc w/ D1-              ears                                              -   Provide adequate nutritious diet         Sources
Ergotism              dopaminergic receptor inhibition &     -   Swelling & reddening of coronary band,            -   Appropriate anti-inflam meds & Abx       - Claviceps purpurea fungal growth
Ergot poisoning       partial agonism of α1-adrenergic &     -   knuckling of pastern, shifting of weight                                                       - Mycelia infected seed heads
                      serotonin receptors                        from one hind limb to the other                                                                   produce dark colored sclerotia or
                                                             -   Can progress to ischemic necrosis &                                                               ergot bodies
                  Sclerotia = A dense mass of branched           sloughing of hooves                                                                            - Contain fungal conidia that replace
                  hyphae, as in certain fungi, that          -   Distinct line of demarcation btwn necrotic                                                        ovarian tissue of infected grass or
                  contain stored food and are capable of         & viable skin                                                                                     cereal grain
                  remaining dormant for long periods.        -   Osteomyelitc changes consistent w/ septic                                                      - Rye & Triticale most suscept (also
                                                                 arthritis                                                                                         wheat, barley, oats, grasses)
                                                                                                                                                                - Tall fescue gras (Festuca
                                                                                                                                                                   arundinacea) infected w/
                                                                                                                                                                   Neotyphodium sp.
                                                                                                                                                                - Many meds are derivatives of ergot

                                                                                                                                                                -   Erogpeptine & ergoline alkaloids
                                                                                                                                                                -   Conc of alkaloids dependent upon
                                                                                                                                                                    seasonal growing cond
                                                                                                                                                                -   Most animals susceptible
                                                                                                                                                                -   Exposure of animals to infected
                                                                                                                                                                -   Concomitant exposure to endophyte-
                                                                                                                                                                    infected fescue
                                                                                                                                                                -   Low & high environ temp predispose
                                                                                                                                                                    to gangrenous ertotism
                  -                                          -                                                     -                                        -   -
Black Walnut      -   unidentified toxin                     -   signs develop w/in 4-12 hrs                       -   remove from source                   -   -   black walnut shavings when used as
                  -   Juglone not responsible for laminits   -   laminitis                                         -   if early – admin AC                          bedding for horses
(Juglans nigra)   -   Crude extract of black walnut          -   elevated body temp                                -   bute                                     -   shavings have to be ingested – packed
                      orally in horses produced              -   ↑HR & RR                                          -   symptomatic & supportive (remove             around feet failed to produce synd
                      decreased blood perfusion to           -   edema of lower limbs                                  shoes, soft bedding)
                      capillaries of laminae                 -   pounding of digital pulses
                  -   Suggestive of ischemia
                  -   Increased sensititvity to
                  -                                          -                                                     -                                        -   -
General mechanisms and manifestations of liver disease                                                                         II. Function of liver
I. Structure of the liver                                                                                                            A. Excretion of waste products; bile formation and secretion; storage of glycogen, lipids, heavy metals,
       A. Lobular model: Lobular unit – based on hexagonal lobule with portal venule, hepatic artery and bile duct at                      and vitamins; synthesis of clotting factors; phagocytosis of foreign material and bacteria.
             edge of lobule (portal triad). Chords of hepatocytes lined by endothelial-lined sinusoids carry blood to                B. Detoxification of substances and preparation for excretion through bile or by kidneys.
             hepatocytes and drain toward central terminal hepatic vein (central vein).                                              C. Metabolic actions and function of hepatocytes vary depending upon location within lobule (and thus,
       1. Periportal region – hepatocytes adjacent to portal triad                                                                         hepatic injury due to toxin exhibited in a regional pattern within lobule).
       2. Midzonal region – hepatocytes midway between portal triad and central vein                                                       1. Portal region – hepatocytes closest to this region are rich in mitochondria and are oxygen
       3. Centrilobular region – hepatocytes adjacent to central vein                                                                            rich.
       B. Acinar model: based on portal triad with acinar unit formed by portal venule and hepatic artery bridging to                      2. Central vein – hepatocytes closest to this region have abundant phase I and phase II
             the next portal triad. Zones of acinar model anatomically similar to regions of lobular unit model.                                 biotransforming enzymes (P450s, reductases, dehydrogenases). This region is low in
       1. Zone 1 – hepatocytes closest to the penetrating venule near portal triad.                                                              oxygen compared to portal region.
       2. Zone 2 – midway between penetrating venules and terminal hepatic vein.                                                     D. Phase I Metabolism
       3. Zone 3 – adjacent to terminal hepatic vein.                                                                                      1. Microsomal enzymes are important phase I enzymes
       C. Blood supply                                                                                                                     2. Toxicants that do not require P450 activity to become toxic are likely to harm peripheral
             1. Hepatic artery – provides oxygen and nutrients to liver.                                                                         lobular hepatocytes (first ones encountered). These toxicoses tend not to be affected by
             2. Portal vein – provides food-laden material and other substances from GI tract for hepatocellular                                 other chemical agents that induce or inhibit P450 enzymes
                    metabolic conversion or removal.                                                                                       3. Older hepatocytes are closer to the central vein and have different and overall more P450
             3. Blood flowing from portal vein and hepatic artery mixes in penetrating venules at periphery of lobule                            activity than peripheral lobular hepatocytes
                    and enters fenestrated endothelial-lined hepatic sinusoids.                                                            4. Agents that require P450 activity to create toxic metabolites often affect primarily
             4. Blood moves along hepatic cords to terminal hepatic venule (central vein).                                                       midzonal or centrilobular hepatocytes.
             5. Blood from terminal hepatic venule eventually connects to posterior vena cava and drains into heart.                             -Agents that induce P450 make these agents more toxic
       D. Hepatocytes                                                                                                                            -Agents that inhibit P450 make these agents less toxic
             1. Hepatic chords composed of rows and columns of hepatocytes.                                                                5. Centrilobular regions are comparatively hypoxic all the time
             2. Hepatic stem cells (oval cells) located near junction of bile canaliculi and bile ducts.                                   6. Agents that cause circulatory failure may cause hypoxic damage centrilobularly and this
             3. Oval cells differentiate toward either hepatocytes or bile ductal epithelium.                                                    may be manifested as necrosis and hemorrhage
             4. As hepatocytes mature, move along cords to centrilobular region.                                                           7. Agents that are specifically bioactivated by P450 in the liver often affect it mid-zonally
             5. Remain in centrilobular region until they die and are displaced.                                                                 and/or centrilobularly
       E. Sinusoids                                                                                                                              -Acetaminophen
             1. Endothelial cells in sinusoids lack a basement membrane.                                                                         -Aflatoxin
             2. Sinusoids fenestrated with numerous pores that allow exchange of fluids and various molecules between                            -Pyrrolizidine alkaloids
                    sinusoids and perisinusoidal space of Disse.                                                                           8. Only a few toxicants concentrate in and thus damage the liver almost exclusively without
             3. Kupffer cells (residential macrophages) reside in sinusoidal spaces and adhere closely to endothelial                            involving bioactivation
                    cells. Ingest and degrade endotoxins and bacteria, and produce inflammatory mediators such as IL-1,                          -Microcystins, Nodularin, Phalloidin (from Amanita phalloides)
                    IL-6, and TNF-α.                                                                                                 E. Phase II Metabolism
             4. Ito cells (satellite cells or fat storage cells) located in perisinusoidal space of Disse. Ito cells contain               1. Conjugation of metabolite to glucuronide, glutathione, sulfates, amino acids, acetate.
                    lipid droplets, store vitamin A, and synthesize collagen. Become myofibroblast-like cells during                       2. Overall, process is to make compounds more water soluble and thus excretable.
                    injury and inflammation and are important in laying down collagen for repair of hepatocellular
       F. Biliary system
             1. Bile canaliculi have tight junctions – prevents leakage of bile into perisinusoidal space of Disse and
                    sinusoids. Toxicant damage to tight junctions can cause separation and damage to bile canaliculi, and
                    leakage of bile salts in circulation.
             2. Bile transported in bile canaliculi to bile ducts by contraction of pericanalicular cytoskeleton. Damage
                    to pericanalicular cytoskeleton can lead to bile stasis and plugging.
             3. Bile ducts leave liver through hepatic duct. Gall bladder (not present in all species) stores bile to be
                    excreted during digestion.
                          -                                                 -                                                  -                                               -                   -
Iron            -   Direct GI irritant – corrosive         Phase 1 (0-6 hrs)                              -   Early – decontam (emesis, gastric       -   Guarded if     Sources
                -   Large does absorbed  TIBC is          - GI upset, vomit, diarrhea, GI bleed              lavage)                                     severe signs   - Multivits, esp prenatal vits
                    exceeded (transferrin)                                                                -   AC binding minimal                                         - Iron supp
                -   Free iron penetrates cells of all      Phase 2 (6-24 hrs)                             -   Precip iron in gut to non-absorbable                       - Iron containing fertilizers
                    tissues                                - Latent per or per of apparent clinical           from w/ MgOH (FeOH)
                -   Increased lipid peroxidation            recovery                                     -   Deferoxamine (desferal) – specific                         -   Ionized iron absorbed into intestinal
                    mem damage to mito, & cell             - Transient phase  animal appears better          chelator for iron - continue until SI                          mucosal cells
                    organelles                                                                                below TIBC or red color (vin rose)                         -   Absorption is energy dependednt &
                                                           Phase 3 (12-96 hrs)                                gone from urine                                                facilitated by trasferrin-like ccarrier
                                                           - Lethargy, recurrence of GI signs             -   Deferoxamine only binds & excretes                         -   Overdose  absorption occurs in
                                                           - Metabolic acidosis, shock                        free iron  inducing iron deficiency                           passive, conc dependent manner
                Lesions                                    - Hypotension, tachycardia, cardio collapse        not a concern                                              -   Iron then transferred to circ & bound
                - Gastroenteritis, gastric ulceration,     - Coag deficits                                -   Symptomatic & supportive for shock,                            to transferrin (produced by liver) for
                   edema                                   - Hepatic necrosis                                 GI irritation/ulceration (IV fluids,                           transport to tissues (esp stored in
                - Hepatopathy – cloudy, swollen            - death                                            A/B, elect, GI protectants)                                    liver, spleen, marrow bound to
                   hepatocytes, portal iron deposition,                                                                                                                      ferritin)
                   massive periportal necrosis             Phase 4 (2-6 wks)                                                                                             -   70% of iron in body in Hb
                                                           - stricture formation from healing GI ulcers                                                                  -   iron store tightly consesrved – little
                                                                                                                                                                             lost in urine, feces
                                                           - serum iron (SI) & TIBC (total iron binding                                                                  -   toxicity depends on iron status of
                                                              capacity) of blood                                                                                             animal
                                                           - if SI approaches or exceeds TIBC  chelate                                                                  -   all species susceptible to iron
                                                           - retest SI in 4-6 hrs b/c variable kinetics                                                                      overload
                                                           - Rads  radioopaque tablets in gut                                                                           -   dependent upon total amt of
                                                           - Deferoxamine challenge  vin rose color to                                                                      elemental iron in product
                                                              urine                                                                                                      -   metallic iron or iron oxide (rust) are
                                                                                                                                                                             not absorbed  NOT toxic
                -                                          -                                              -                                           -                  -
Acetaminophen   -   normally APAP is conjugated to         Cats                                           -   decontam – emesis, AC/SC                -                  -   OTC preps
                    suflate & excreted                     - Onset several hours after exposure           -   N-acetylcystine (Mucomyst) – provides                      -   Rapid absorption from gut
Paracetamol,    -   if sulfation pathway is exhausted,     - Depression, anorexia, vomit,                     -SH groups fro binding of reactive                         -   Undergoes Sulfate & glucuronide
APAP                then conjugation to glucuronide        - methemoglobinemia, cyanosis,                     metabolites & acts as a glutathione                            conjugation
                -   if extremely large exposures or if     - tachypnea, hyperpnea                             precursor for formation of more                            -   Glutathione scavenges reactive
                    species deficient in glucuronidation   - Weakness                                         glutathione (oral is preferred route,                          metabolites
                    (Cat)  glucuronide path               - Edema of face, paws                              not right after AC)
                    exhausted                              - High doses  diffuse hepatic necrosis        -   Ascorbic acid – antioxidant                                Cats
                -   APAP then undergoes metabolism                                                        -   Cimetidine or ranitidine – reduce                          - Deficient in glucuronyl-s-
                    by hepatic P450 enzymes to             Dogs                                               metab of APAP                                                transferase (enzyme required for
                    produce toxic NAPQI                    - Onset delayed 1-3 days                                                                                        glucuronide conj)
                -   NAPQU binds to glutathione             - Reduced activity & responsiveness                                                                           - Feline Hb contains more –SH
                    (GSH) & excreted in urine                (depression)                                                                                                  groups  more susceptible to
                -   If glutathione becomes depleted,       - Anorexia, vomit, abd pain,                                                                                    attack by oxidizing agents
                    then NAPQI binds to cell               - Icterus, shock                                                                                              - Methemoglobinemia
                    macromolec (sulfhydryl-containing      - High dosages  methemoglobinemia
                    proteins)  disrupt normal             - Centrilobular hepatic necrosis
                    function of cell  cell death
                                                           Clin path
                                                           - ↑methemoglobin in cats – put drop of blood
                                                              on white filter paper (appear brown)
                                                           - ↑liver enz in dogs
                -                                          -                                              -                                           -                  -
Coal Tar        -   detoxified by glucuronidation          Clay pigeon induced liver lesions in swine       -   Assess mucosal damage – do not use         -                 -   coal tar shampoos
Pitch           -   CATS & NEONATES of all species         - Enlarged liver, mottled, engorged                  emetics or lavage if damage is evicent                       -   roofing tars
Clay Pigeons        are deficient on certain glucuronly    - Centrilobular hyperemia, fatty degeneration    -   AC, saline cathartic if time frame                           -   clay pigeon targes
Phenolics           transferases  predispose to              & necrosis                                        indicates value                                              -   phenol disinfectants
                    toxicity                                                                                -   Wash exposed skin w/ glycerine or                            -   Lysol
                -   uncoupling of oxidative                Diagnosis                                            polyethylene glycol then bathe w/ gentle                     -   Cresols, hydroxytoulenes
                    phosphoryation  fevers                - Appropriate exposure, clin signs, lesions          liquid dish det                                              -   Tricresol
                -   stimulated respiratory center         - Lamp oil odor to breath                        -   Demulcents, symptomtic, supportive                           -   Naphthol, menthol, thymol, guaiacol
                    resp alkalosis                         - Lab analaysis of source material, stomach      -   Aetylcystine if needed fro
                -   liver failure (inability to mobilize      contents, serum, urine, kidney                    methemoglobinemia
                    glucose) & shock  metabolic                                                            -   Fluids, symptomatic, supportive
                -   liver & kidneys damaged
                -   highly conc phenol & cresol 
                    “cooked egg white” (protein precip)
                    effect on mm (chemical cautery)
                -   swine die suddenly
                -   methemoglobinemia
                -                                          -                                                -                                              -                 -
Cycad Palms     -   CYCASIN – major glysodie present       Dogs                                             -   Early decontam – emesis & AC/SC            -   Good if       -   ornamental yard & garden plants in
Sago Palm           in Cycads                              - Vomiting (+/- blood) , diarrhea, anorexia      -   GI protectants                                 early             warm southern states (FLA, AZ)
                -   GI irritation & Hepatic Necrosis       - Depression                                     -   Fluids & elect support                     -   Poor to       -   ornamental potted houseplants
Cycas sp        -   BMAA (β-methylamino-L-alanine) –       - Seizures secondary to hepatic damage           -   Symptomatic treat                              guarded       -
Macrozamia sp       neurogoxic aa                          - ↑serum hepatic enz (ALT, AST, ALP)                                                                once clin
                -   Unidentified toxin – axonal            - hyperbilirubinemia & elect abnormalities                                                          signs begun
                    degeneration in CNS
                Lesions                                    - Lethargy, anorexia, wt loss, gastroenteritis
                - Hemorrhage & necrosis of GIT             - Leukocytosis
                - Marked centrilobular & midzonal          - Hypoalbuminemia
                   necrosis in dogs                        - ↑AST, SLP, GGT
                - Megalocytosis, periacinar necrosis &
                   fibrosis in ruminants                   Cattle
                - Hepatic encephalopathy = spongy          - wt loss, weakness, ataxia,
                   degen of CNS, demyelination &           - paresis (zamia staggers)
                   axonal degeneration in brain, SC,       - leukocytosis, hypoalbuminemia
                   Dorsal root gang                        - ↑AST, SLP, GGT

                                                           - Hx,of exposure & clin signs
                                                           - ID plant material in GI contents
                -                                          -                                                -                                              -                 -
Aflatoxins    -   AFLATOXIN B1                           -   determined by dose & duration of exposure        -   remove source                            -   -   Aspergillus
              -   reactive metabolites bind w/ cell                                                           -   symptomatic & supportive depending           -   Primarily in damaged plant tissues
X disease         components to disrupt normal           acute (uncommon)                                         on clinical condition of animal                  (drought, insect damage)
Hepatitis X       catabolic & anabolic processes         - anorexia, depression, weakness, dyspnea                                                             -   Considered a Storage mold, but can
              -   result: disruption of organ fxn,       - emesis, diarrhea (blood & mucus)                   Control                                              occur in field
                  carcinogenesis,                        - hypothermia, convulsions, epistaxis, icterus       - insitiute procedures to prevent crop           -   Mold growth best w/ high moisture &
                  immunosupporesion, mutagenesis,                                                               damage during growth & harvest                     warm temp
                  teratogenesis                          Chronic (most common)                                  (insect control)                               -   Fluorescence in UV light (blue,
              -   rumen microbes may detoxify, but       - subtle onset                                       - dry corn to prevent seed coat damage               green)
                  aflatoxin may have deleterious         - liver disease                                      - ammoniantio of feedstuffs – hydrolysis         -   Metabolites found in milk & other
                  effect upon microbes                   - ↓wt gain, rough hair coats                           of lactone ring of aflatoxin B1 to less            tissues
              -   B1, B2  M2 & M2 (metabolites)         - progress to anemia, jaundice, anorexia,              toxic products                                 -   Aflatoxin B1 – most toxic &
                                                           depression                                         - NovaSil+ - hydrated Sodium Calcium                 carcinogenic
                                                         - GI upset w/ hemorrhage & ascites                     aluminosilicate feed additive – anti-          -   Found in crops w/ high energy
                                                                                                                caking agent in complete livestock &               content: corn, peanuts, cottonseed,
              Lesions                                    Clin Path                                              poultry rations  recudde caking &                 rice, sweet potatoes
              acute high dose:                           - ↑liver enz                                           enhance flow properties  adsorbant            -   TROUT & DUCK very sensitive
              - hemorrhage into intestines, on                                                                  to bind aflatoxin & reduce toxic effects
                 pericardium, fat, muscle, SQ tissue     Diagnostics                                            (does not work on other mycotoxins)            -   Rapidly & completely absorbed from
              - disorganizaitno of hepatocytes &         - demonstration of toxigenic fungus insufficient                                                          SI
                 vacuolization                              for diagnosis                                                                                      -   Binds to albumin in blood
              - swelling of cells, centrilobular         - detect aflatoxin B1 in feedstuffs or liver                                                          -   Accum in liver, kidney, marrow,
                 congestion & necrosis                   - black light test – pos test  kojic adic (fungal                                                        lungs
              subchronic exposure                           metabolite)  does not indicate presence of                                                        -   Highest conc in liver
              - prolive of bile duct cells                  toxin                                                                                              -   Elim in bile, rine, feces, milk, eggs
              - granular & vacuolated hepatocyte                                                                                                               -   Aflatoxins do not accum in tissues
                 cytoplasm                                                                                                                                     -   Biotransformed in liver, kidney, SI
              - nodules of regenerating liver cells                                                                                                                (binding of eposide to cell
              Chronic exposure                                                                                                                                     macromolec resoponsive ffor cell
              - Diffuse fatty changeof liver                                                                                                                       injury & death),
              - Prolif bile ducts                                                                                                                              -   can bind DNA, RNA, prot
              - Distorted architecture of liver
              - Centrilobular accum of lipids                                                                                                                  -   tox depends on species, health &
                                                                                                                                                                   nutrition of animal, duration on
              -                                          -                                                    -                                            -   -
Cocklebur     -   CARBOXYATRACTYLOSIDE                   -   Death as soon as a few hrs or dz may be          -   symptomatic & supportive                 -   -   water sol, readily absorbed, acts
              -   Inhibits ADP/ATP carrier in mito           protracted fro 2-3 D                                                                                  quickly
Xanthium      -    inhibits oxidative phosphorylation   -   Depression, abd pain & tenderness,                                                                -   highest conc in seeds & 2 leaf
strumarium                                                   anorexia, salivation, Vomit, dyspnea                                                                  cotyledons
              Lesions                                    -   Fasciculaitons, extensor rigidity, spasmodic                                                      -   becomes less toxic w/ age of plant
              - GI irritation                                contractions of limbs & neck muscles,
              - Firm pale liver                              convulsions, opisthotonus
              - Haptic centrilobular hemorrhage &        -   Paddling, prostration, coma, death
              - Acute nephritis – milkd to mod           Clin path
                 tubular degen                           - ↑liver enz
                                                         - HYPOGLYCEMIA
              -                                          -                                                    -                                            -   -
Pyrrolizidine       -   toxic PYRROLES formed & react w/              Acute toxicosis                               -   no specific treat                           -   poor           -   Senecio sp, Crotalaria sp,
Alkaloids               cellular nucleophilic cmpds (proteins         - Acute liver fail                            -   chronic progressive process that is often   -   animals            Heliotropium sp, Amsinckia sp,
                        & nucleic acids)                              - Anorexia, depression, icterus, acites           subclinical                                     exhibiting         Cyoglossum sp, Echium sp,
Seneciosis          -   adducts responsible for cytotoxic &           - Serum biochem  massive elevations          -   avoid pastures w/ pyrrolizadine-                signs rarely       Symphytum sp
Hepatic cirrhosis       antimitotic effects of poisioning               hepatic enzymes, bilirubin bile acids           containing plants                               recover
Venoocclusive dz    -   pyrrolic adducts may be recycled                                                                                                                              -   Require bioacitvation (liver P450s) to
                        progressive hepatic damage                    Chronic toxicosis                             Control                                                                toxic dehydropyrrolizidine alyaloids
                                                                      - May take mons or years for signs to         - inspect pastures & feed for plant contam                         -   Toxicity & tissue damage are pyrrole
                    Lesions                                             develop                                     - herbicides                                                           specific – hepatic vs. extrahepatic
                    - dose dependent hepatocytes swelling            - General hepatic malfxn: poor doers,                                                                            -   PIGS mot sensitive
                       followed by cell degen, necrosis, cell           unthriftiness, photosensitivity, icterus    Consideration for humans drinking                                  -   Followed by chickens > cattle &
                       death                                          - ↑susceptibility to other hepatic dz         comfrey tea:  potential for hepatic                                   horse > rats > mice > sheep & goats
                    Acute intox, high doses                             (ketosis, lipidosis)                        damage                                                             -   Tox dependent upon liver & gut
                    - pan-lobular hepatocell necrosis w/              - major stresses (preg, lactation)                                                                                  (rumen) metab – individual for
                       hemorrhage & min inflam                          clinical liver failure                                                                                             species
                    Chronic intox, lower doses & longer               - serum biochem  normal for several                                                                             -   YOUNG & NURSING animals more
                    duration                                            mos or only mild elevations in liver                                                                               suscept than adults
                    - focal hepatocyte necrosis, minimal                values                                                                                                         -   MALE RATS more sens than females
                       peribiliary fibrosis, milkd bile duct prolif                                                                                                                    -   POORLY NOURISED animals more
                    - w/ time  lage megalocytes, hepatocyte          diagnosis                                                                                                            likely to develop disease
                       necrosis w/ inflam, fibrosis, cirrhosis        - based on hx, clin signs, tissue lesions                                                                        -   Animals w/ HIGH HEPATIC
                    - reactive pyrroles alkalate macromolec in        -                                                                                                                    GLUTATHIONE levels more
                       hepatocyte (DNA)  impair cell division                                                                                                                             RESISTANT to PA dz
                    - hapatocyte unable to divide, but                                                                                                                                 -   PA conc in plants vary w/ environ
                       continues to grow                                                                                                                                                   factors
                    - nucleus & cyto expand
                       (hepatocytomegaly, karyomegaly)
                    - necrosis triggers reparative response 
                       bile duct prolif
                    - necrosis results in fibrosis

                    **3 main lesions**:
                    - hepatocytomegaly
                    - fibrosis
                    - bile duct prolif
                    -                                                 -                                             -                                               -                  -
Blue-Green          - bidn covalently to prot phosphatases            -   acute death possible from neurotoxins     -   Early decontam – emesis, AC (if             -   Poor           -   rapid absorb of free toxins in gut
Algae                   dysfxn of intracell regulatory prot          -   blood cholinesterase activity depressed       exposure witnessed)                         -   Rapidity &     -   transported to liver via bile acid
                    - microcystins disrupt intermed                                                                 -   Hepatic effects – symptomatic &                 severity of        carriers
Cyanobacteria          filaments, microtubules,                       hepatic damage                                    supportive for hemorrhagic shock                hepatic        -   warm weather, increased nutrients in
                       microfilaments  disturbances in cell          - lethargy, vomit, diarrhea, GI atony                                                             effects            body of water, wind
Anabaena,              cytoskeleton  collapse of cell                - weakness, pae mm,                           Control                                                            -   most common in late summer, early
Aphanizomenon,      - microcystins induce apoptosis in                - ↑liver enz                                  - Avoid animal contact w/ water                                        fall
Oscillatoria,          variety of mammalian cells                     - death by 24 hrs, but usu delayed            - Provide alternative water supply                                 -   runoff from fertilized fields 
Microcystis,        - neurotonix anatosin-a & anatoxin-a(s)           - survivors  secondary                       - Copper sulfate in ponds as algaecide                                 elevate nitrogen & phosphorus
Nodularia                                                                photosensitization                           (keep animals away from water for                                    content of water
                    Lesions - liver:                                                                                  several days to allow for degradation of                         -   wind blows algal bloom toward
                     - enlarged, dark, congested                      Diagnostic                                      toxins)                                                              shoreline  ↑chance of ingestion
                     - centrilobular to midzonal necrosis &           - ID bacteria – water from area w/ algae,
                        hemorrhage                                       necropsy samples, gut contents
                     - lethal intrahepatic hemorrhage due to          - ID toxin in water samples, algae, gut
                        cytoskeletal disruption                          contents, liver
                     death due to hemorrhagic shock
                    -                                                 -                                             -                                               -                  -
Lantana             -  LANTADENE A & B: TRITERPENE                   -   RUMINANTS most common                        -   AC to control absorption of toxins        -                  -   southern warmer areas, ornamental in
                       ACIDS                                                                                          -   Supportive care: fluids, glucose, elect                          northern climates
                    Induce intrahepatic cholestasis                  Acute exposure                                   -   Provide shade
                    - Slow & prolonged absorption from gut           - Sings by several hours
                       ( continuous soruce of toxin)                - Depression, anorexia, ↓rumen motility,
                    - Biotransformed in liver & excreted in            constipation
                       bile  damage bile canalicuar mem &           - Progress by 2-3 D  icterus & skin
                       microvilli                                      changes related to photosensitization
                    -  ↓ATPase activity
                    -  closure & blockage (backup) of bile          Chronic exposure
                       flow                                          - Signs develop over several weeks
                    - retention of bilirubin & phylloerytrin         - Photosensitization, cracking &
                                                                       desquamation of skin
                    Lesions                                          - Inflam of sclera, clouding cornea, ↑
                    - swollen, orange colored liver w/ enlarged        sensitivity of eyes to bright light
                    - periportal degen, portal fibrosis, bile duct
                       hyperplasia, mild to mod centrilobular
                    - edema of wall of GB
                    - swollen kidneys, perirenal edema
                       possible, tubular necrosis w/ casts
                    -                                                -                                                -                                             -                  -
Sesquiterpene       - SESUITERPENE LACTONES – strong                 Acute (least common) – ingest plants for a few   -   remove animals from source                -   poor once      -   Helenium, hymenoxis
lactone                irritants to GIT                              days                                             -   provide adequate nutrients                    signs
containing plants   - Profound effects on metabolism by              - Depression, anorexia, ruminal atony, bloat,    -   symptomatic & supportive                      develop        -   All species at risk
                       binding to –SH groups  metabolic                abd pain,                                                                                                      -   SHEEP most likely tot eat plants &
Bitterweeds            acidosis & hypoglycemia                       - Wheezing, coughing, green saliva,              Control                                                              greatest risk
Sneezeweeds                                                          - arched back, Tremors, convulsion, death        - provide good feed                                              -   Very bitter tasting – hungry animals
Spewing dz                                                           Subacute
                                                                     - Similar but milder signs
                                                                     - Regurgitation & vomit of greenish material
                                                                        (“spewing sickness’)
                                                                     - death
                                                                     Chronic - ingestion of plant for weeks or mos
                                                                     - poor body condition w/ weight loss
                                                                     - dehydraion
                    -                                                -                                                -                                             -                  -
Alsike Clover       -   toxic principle unknown                      - Signs can develop 2-4 wks after initial        -   No specific treat                         -   Excellent      -   found in pasture mixes
                    -   Plant fungus Cymodothea trifolii may            exposure                                      -   Symptomatic & supportive                      for those      -   ONLY HORSES susceptible
Trifolium               play role in dz                              - Photosensitization due to hepatic damage                                                         exhibiting     -   Cool, wet spring predisp to
hybridum                                                             - Neuro signs assoc w/ hepatic                   Control                                           only               development
                    MOA – unknown                                       encephalopathy                                - Do not allow access to plant in diet            photosensiti   -   Fresh pasture & baled hay assoc w/
Big liver dz                                                         - Elevations in hepatic enzymes, serum                                                             zation             dz
Dew Poisoning       Lesions                                             ammonia, bile acids, total bili                                                             -   Poor for
Trifoliosis         - Bile duct prolif & perilobular,                - Poor appetite, weight loss, weakenss, poor                                                       those
                       centrilobular, periportal fibrosis               hair coat                                                                                       exhibiting
                    - Fibrous ct spares sinusoids but constricts                                                                                                        hepatic
                       surrounding functional parenchymal            Diagnosis                                                                                          encephalopa
                       tissue                                        - By hx of exposure & clin signs & lesions                                                         thy
                    - Grossly – liver normal, enlarged, or

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