Nephrotoxicants

1
Nephrotoxicants
2
Oxalate toxicosis -1

• Beta vulagaris (beet)
• - tops high in oxalates
• Chenopodium album (lambs quarters)
• - both oxalates and nitrates
• Halogeton glomeratus - arid, high saline soils
• - oxalate peak in fall, persists through winter
• Rheum rhaponticum (rhubarb)
• - leaves contain anthroquinone glycosides, too
• Sarcobatus vermiculatus (greasewood)
• - western range, oxalates all parts,
• more d as plant matures

Halogeton
Sarcobatus
3
Oxalate toxicosis - 2

• Soluble oxalates plus serum calcium ?calcium
  oxalate
• Ionized calcium depleted ?functional hypcalcemia
• Crystallization in renal tubules ?fatal renal
  tubular toxicosis
• One-time consumption sufficient to cause toxicosis

• Clinical signs
• muscle twitching, mild seizures, prostration,
  death possible
• oligura, depression, vomiting, azotemia,
  depression, hyperkalemia, cardiac failure
• if dont die, may develop chronic tubular
  nephrosis with polyuria and hyposthenuria
• Treatment
• limewater (calcium hydroxide) to ppt. oxalate in
  intestinal tract

4
Cholecalciferol (vitamin D) toxicosis

• Cestrum diurnum (night-blooming jessamine)
• S and SE UStropical and subtropical US
• Solanum malacoxylon
• HI and S. America

• Dx - clinical and lab
• vitamin D excess ? hypercalcemia ? soft tissue
  mineralization, renal tubular necrosis
• depression, anorexia,vomiting, PU/PD, azotemia
• serum calcium gt2mg/dl

5
Quercus spp. (oak)

• polyhydroxyphenolic -gallotannin, in both leaves
  and acorns
• common in cattle and calves, less sheep horses

• Clinical signs-
• anorexia, dullness, rumen atony, constipation,
  feces dark w/mucus film (or tarry stool)
• weakness, prostrate 3-7 d post-exposure,
  mortality may be high
• icterus, hematuria, dehydration, polyuria,
  hyposthenuria
• abortion

6
Quercus spp. (oak)

• Treatment-
• 10-15 calcium hydroxide in grain to aid
  precipitation of oak tannins and reduce mortality
  in cattle
• Lesions-
• gastroenteritis, ascites, hydrothorax
• subserosal petechial or ecchymotic hemorrhages
  over surface of gi tract
• gelatinous blood-tinged edema around kidneys,
  which are enlarged, pale, hemorrhagic
• coagulative necrosis of proximal convoluted
  tubules

7
Amaranthus retroflexus (redroot pigweed)

• moist disturbed soils, U.S.
• accumulate nitrates and oxalates, but these dont
  cause toxicosis

• Clinical signs (swine) -
• weakness, trembling, incoordination, knuckling of
  pastern joints, paralysis of hind limbs, coma,
  death
• elevated BUN, creatinine, serum K, bradycardia
• survivors may have chronic interstitial fibrosis
  in kidneys but appear clinically normal
• (Signs in cattle like oak poisoning)

8
Hemerocallus, Lilium (daylily,
lilies)

• cultivated, escapees
• assoc. w/renal tubular necrosis in cats
• all parts nephrotoxic

• Clinical signs -
• anorexia, depression, anuria
• acute renal tubular necrosis
• ingestion is medical emergency!

9
Cardiotoxicants
10
Andromedotoxicosis (grayanotoxicosis)

• Kalmia (laurel, lambkill, calfkill)
• - threat to browsing animals
• Rhododendron (rhododendron, azalea)
• - wild and cultivated

• Pieris japonica (Japanese pieris)

11
Andromedotoxicosis - 2

• diterpenoid compounds modify Na channels,
  leading to prolonged depolarization and
  excitation
• favors Ca movement into cells and positive
  inotropic effect

• Clinical signs
• salivation, burning sensation in mouth, followed
  by emesis, diarrhea, muscular weakness, impaired
  vision
• bradycardia, hypotension d.t. vasodilation, av
  block
• Treatment
• atropine
• isoproterenol or sodium channel blockers (e.g.,
  quinidine)

12
Digitalis glycoside poisoning
Apocynum (dogbane, hemp)?
? Convallaria majalis (lily-of-the-valley) -
toxin in flowers, leaves, seeds, not berries
Digitalis purpurea (foxglove) - digitalis
glycosides all parts ?
? Nerium oleander (oleander)- highly toxic, few
oz. kills horse
13
Cardiac Glycoside Poisoning - 2

• conduction block and eventual asystole
• toxins readily absorbed, enterohepatic recycling

• Clinical signs
• initially gi - vomiting, abdominal pain, moderate
  to severe diarrhea (sometimes hemorrhagic)
• bradycardia, arrhythmias, ventricular premature
  systoles, paroxysmal tachycardia, complete heart
  block, asystole
• depression and coma d.t. cardiac insuffienciency
• Treatment
• monitor and treat hyperkalemia
• phenytoin may assist av conduction and ? heart
  rate
• antidigitalis antibody fragments for severe
  toxicosis

14
Digitalis-like Glycoside Poisoning - 2

• Aconitum napellum (monkshood)
• aconitine and related alkaloids
• toxin in entire plant

• Clinical signs
• oral and pharyngeal inflammation, salivation,
  nausea, emesis, blurred vision
• hypotension, cardiac arrhythmias, weakness prior
  to death
• Treatment
• as for cardioactive glycosides

• Asclepias (milkweed) - see neurotoxicants

15
Taxus cuspidata, T. baccata (Japanese yew,
English yew)

• taxine alkaloids (A and B) inhibit
  depolarization in heart
• whole plant except red aril (fruit) is highly
  toxic
• 6-8 oz. kills horse or cow

• Clinical signs
• trembling, muscle weakness, dyspnea, collapse
• arrhythmia, bradycardia, diastolic heart
• Treatment
• atropine early may help

16
Zygademus (death camas)

• Great Plains and Rocky Mtn. states
• steroidal alakloid - zygadenine or zygacine
• all parts of the plant
• one of first green plants available in spring

• Clinical signs
• salivation, nausea, vomiting, rapid pulse,
  stiffness, trembling, ataxia, weakness,
  recumbency, coma, death

17
Toxicants that alter peripheral circulation
18
Berteroa incana (hoary alyssum)

• central U.S., pastures, hay fields, waste areas
• toxic principal unknown

• Clinical signs
• moderate to severe laminitis
• edema of lower limbs

19
Festuca arundinacea (Kentucky 31 tall
fescue)

• major forage grass in SE U.S.
• endophytic fungus Acremonium coenophialum
• ergopeptide alkaloids (esp. ergovaline) found in
  leaves and seeds
• can purchase endophyte-free strains
• 3 clinical syndromes
• no treatment except for pain

20
Festuca arundinacea (Kentucky 31 tall
fescue)

• Fescue foot
• dry gangrene of extremities (feet, tail, ears)
• cold weather accentuates severity
• lameness often begins in rear limbs in cattle
• Bovine fat necrosis
• large masses of hardened fat in abdomen
• when pure stands heavily fertilized
• Summer syndrome or summer slump
• - most economically damaging
• - lower weight gains, reduced milk production,
  heat intolerance
• - ? postpartum interval, ? pregancy rates

21
Juglans nigra (black walnut)

• shavings or sawdust occasionally used as animal
  bedding
• horses at greatest risk
• toxic principle unknown

• Clinical signs
• w/in 24 hrs of exposure, rapid onset of
  laminitis, digital pulse, distal edema of the
  limbs, polypnea, elevated temperature
• necrosis of the dorsal laminae may occur

22
Pulmonary toxicants
23
Plant sources of pulmonary toxicants

• Brassica (rape, canola)
• glucosinolates hydrolyzed to isothiocyantes in
  stomach or rumen
• Ipomea batata (sweet potato)
• Fusarium solani produces ipomeanol, mycotoxin
  causing acute pulmonary emphysema in cattle
• Perilla frutescens (purple mint, beefsteak
  plant)
• Perilla ketone similar to ipomeanol

24
Pulmonary toxicants - 2

• Clinical signs
• dyspnea, cyanosis from anoxia
• cattle extend head, open-mouth breathe
• disorientation, belligerance, recumbency, death
  within a few hours to 1-2 days
• Lesions
• massive pulmonary emphysema
• air may infiltrate subcutaneous space voer thorax
  and behind scapulae
• Type I cells absent or necrotic, replacement by
  type II cells gives lung appearance of
  adenomatosis

25
Plants that affect the blood

• Hematopoeitic depression
• Hemolysis
• Hemorrhage
• Methemoglobinemia
• Cyanide toxicosis

26
Pteridium aquilinum (bracken fern)

• forested areas of N. U.S.
• lactone - ptaquiloside responsible for effects
  on blood
• all parts are toxic
• thiaminase activity in horses

• Clinical signs (cattle) - aplastic anemia,
  granulocytopenia, thrombocytopenia urinary
  bladder neoplasms w/chronic exposure
• Dl batyl alcohol limited value
• Clinical signs (horses) - thiamine deficiency,
  ataxia, weakness, paralysis, NO blood effects
• thiamine injections may help
• Prognosis poor in advanced cases

27
Acer rubrum (red maple)

• natural in East, cultivated elsewhere
• toxic principle unknown
• causes acute hemolysis in horses
• fresh, wilted, dried leaves

• Clinical signs
• depression, icterus, anemia, hemoglobinemia,
  hemoglobinuria
• polypnea, tachycardia, cyanosis may be present
• low PCV, mild methemoglobinemia, Heinz bodies,
  hyperbilirubinemia, occ. increased
• Whole blood transfusion may be lifesaving.

28
Allium spp. (onions, garlic)

• N-propyl disulfide denatures hemoglobin
• toxicant present in bulb
• cattle more susceptible than other species
  dogs, horses, rabbits, too.

• Clinical signs
• weakness, polypnea, icterus, hemoglobinuria,
  cyanosis
• Whole blood transfusion may be lifesaving

29
Lespedeza sericea, Melilotus officinalis and M.
alba (sweetclover)

• legume cover or forage crops
• coumarin glycosides dimerized to dicoumarol by
  molds that invade plants that are improperly
  cured or in molded silage
• dicoumarol is competitive inhibitor of vitamin K
  epoxide reductase so interferes with production
  of clotting factors
• cattle most often poisoned d.t. exposure

M. alba

• Clinical signs
• acute blood loss, subcutaneous hematomata,
  anemia, epistaxis, hemorrhagic diarrhea, abortion
  form placental hemorrhage
• Treatment
• transfusion, phytonadione (vitamin K1)

30
Methemoglobinemia from nitrate-containing plants
-1

• plants use nitrite to form vegetable protein from
  nitrate through action of nitrate reductase
• nitrates accumulate in stalks and leaves
• factors affecting nitrate accumulation in plants
• nitrate, ammonia supply
• moisture needed for uptake
• acid soils favor absorption
• (continued next page)

Nitrate-containing plants Amaranthus retroflexus
Zea mays (corn, maize) Avena sativa
(oats) Chenopodium album Beta vulgaris
(beets) Sorghum
31
Methemoglobinemia from nitrate-containing plants
-2

• factors affecting nitrate accumulation in plants,
  contd.
• nitrate reductase activity
• need molybdenum, sulfur, phosphorus, adequate
  light
• frost damage interferes for several days
• drought reduces activity
• phenoxy acetic herbicides increase growth rate
  and nitrate accumulation, highest 3-5 d
  post-application
• plant species and phase - highest prior to
  flowering
• ensiling reduces nitrate to nitrite and then
  ammonia

32
Methemoglobinemia from nitrate-containing plants
- 3

• forage exceeding 1 nitrate may cause acute
  toxicosis
• LD50 for cattle is 1g/kg
• LD50 for ruminants is 0.5g/kg body weight
• ruminants can adapt to higher nitrate with
  time
• tolerance is increased by high-quality diet with
  readily available

33
Methemoglobinemia from nitrate-containing plants
- 4

• nitrite ion oxidizes ferrous iron in hemoglobin
  to ferric state, forming methemoglobin, which is
  incapable of carrying oxygen
• clinical toxicosis at 30-40, death at 80-90
  methemoglobin
• results in abortion in pregnant females within
  2-3 d as result of fetal death from anoxia

34
Methemoglobinemia from nitrate-containing plants
- 5

• clinical signs
• anxiety, polypnea, dyspnea, rapid, weak pulse
• weakness, ataxia, low exercise intolerance
• lab diagnosis
• analysis of forage, hay, water for nitrates
• methemoglobin , must stabilize blood with
  phosphate buffer (1pt blood 20 pts buffer)
• gt30 ppm nitrate in ocular fluid diagnostic
• lesions
• dark brown blood staining of tissues, cyanosis

35
Methemoglobinemia from nitrate-containing plants
- 6

• treatment
• methylene blue, except in cats
• may need to be repeated several times because
  nitrite continues to be formed in the rumen
• large doses of antibiotics may inhibit ruminal
  reduction of nitrate to nitrite

36
Cyanide toxicosis - 1

• Factors influencing cyanide accumulation in
  plants
• species
• pitted fruits (peaches, apricots, cherries,
  almonds)
• pome fruits (apples, pears)
• grasses (Johnson, sorghums, corn)
• elderberry
• legumes (birdsfoot trefoil, white clover, vetch
• portion of plant
• cyanogenic glycosides in seeds, leaves, bark,
  stems, and fruit (in order from greatest to least)

37
Cyanide toxicosis - 2

• Factors influencing cyanide accumulation in
  plants - contd.
• phase of plant growth
• young rapidly growing plants or plants undergoing
  regrowth highest
• environmental factors
• stresses increase glycoside formation, damage to
  cell walls causes release of ?-glycosidase, which
  liberates free cyanide
• soil conditions high N and low Phos favor
• temp, light, soil pH through effect on growth

38
Cyanide toxicosis - 3

• cyanide combines w/iron in cytochrome oxidase,
  blocking cellular respiration
• rhodanese naturally detoxifies if thiosulfate
  available
• cyanide thiosulfate rhodanese -gt thiocyanate
  -gt excreted in urine
• ruminants more susceptible because of
  ?-glycosidase in rumen

39
Cyanide toxicosis - 4

• Diagnosis
• Clinical signs
• initial excitement, muscle tremors w/in 30
  minutes of ingestion
• blood and tissues cherry red (blood is oxygenated
  but cant release oxygen to cells)
• Polypnea, dyspnea, chronic convulsions, coma,
  death

40
Cyanide toxicosis - 5

• Diagnosis
• Laboratory
• plants may be analyzed for cyanide
• urinary thiocyanate elevated
• picric acid-impregnated paper for qualitative
  test
• Lesions
• blood clots slowly or not at all
• bitter almond smell exuded from rumen
• subendocardial, subepicardial hemorrhages
• abomasum, intestine congested, petechiae

41
Cyanide toxicosis - 6

• Treatment
• goal is to break cyanide - cytochrome oxidase
  bond
• sodium nitrite plus thiosulfate
• sodium nitrite causes cyanmethemoglobin to form,
  releasing bond
• thiosulfate assists natural detoxification
• cobalt salts recommended but generally not used

42
Plants that affect reproduction

• Abortion
• Clinical estrogenism
• Teratogenic effects
• Agalactia

43
Pinus ponderosa (Western yellow pine, ponderosa
pine), P. taeda (loblolly pine)

• P. ponderosa, NW mtns. of U.S.
• P. taeda, E and SE U.S.
• unidentified agent in fresh and dried needles
• causes abortion in cattle after substantial
  intake for several days

• Clinical signs
• abortion in the last trimester of pregnancy
• often edema of the udder and vulva in dam
• retained placentas and metritis

44
Xanthocephalum (Western broomweed)

• SW U.S. Texas to California to Idaho
• saponin
• ruminants, swine, rabbits are susceptible

• Clinical signs
• acute
• depression anorexia, nasal discharge, diarrhea
• chronic
• abortion in cattle in the first 2/3 of gestation
• aborted calves are small
• dam usually has a retained placenta

45
Trifolium repens (subterranean clover), T.
subterraneum, Medicago sativa (alfalfa)

• isofalvone estrogens genistein and formononetin
  cause signs related to Trifolium
• coumestrol produced by alfalfa is moderately
  estrogenic

• Clinical signs
• reduced transport and fertility of ova
• cystic hyperplasia of the cervix
• feminization
• reduced libido in males

46
Teratogenic effects

• Table in Osweiler

47
Agalactia

• Claviceps purpurea (ergot)
• Festuca arundinacea (Kentucky 31 tall fescue)

48
Plants that affect the skin

• Primary photosensitization
• Physical damage

49
Primary photosensitization

• occurs when photodynamic agent is
• directly ingested (or injected)
• absorbed through skin
• produced by biotransformation
• major effects in the skin, other organs usually
  spared
• prompt removal of photosensitizer, supportive Rx
  often results in recovery with few sequelae

50
Primary photosensitization

• Cymopterus watsonii (spring parsley)
• desert AZ and Utah
• xanthotoxin and begapten
• Fagopyrun esculentum (buckwheat)
• fagopyrin in both green and dry plant
• Hypericum perforatum (St. Johnswort)
• hypericin, red pigment
• cattle more susceptible
• than sheep

51
Physical damage to mouth and skin

• Table in Osweiler