Ruminant Toxicology
Ruminant Toxicology
Acknowledgements
Dr. Sarah Humphreys DVM DACVIM (LAIM)
Ailbhe King MVB DACVIM (LAIM)
Learning Objectives
Outline a basic approach to diagnosis and treatment of ruminant intoxication.
Recall the toxic principles and clinical signs related to the following toxicants:
Oleander
Ionophores
Gossypol
Rhododendron
Perilla Mint
Moldy Sweet Potato
Pyrrolizidine Alkaloids (PA’s)
Copper
Thiaminases
Ponderosa Pine
Lupine
Nitrates
Lead (Organophosphates will be covered for NAVLE but not in lecture).
History
Onset and progression of signs:
Duration of the problem in the herd.
If found dead, last seen alive and healthy.
Any recent threats or malicious acts.
Changes in exposure:
Recent changes in sources of feed, forages, or pastures.
Weed invasions into forage or grain crops and weed seeds in grain or feed.
Recent pesticide use; check for tags/bags for identification.
Access to construction materials or outside services (lawn care, tree planting, etc.).
Access to old machinery, automotive products, treated lumber, and other potential toxic sources.
Dietary data:
Type of feed and hay.
Presence of molded or spoiled feed/hay.
Recent changes in total diet or specific feed ingredients.
Pasture type, including abundance, weed contamination, and presence of trees or brush.
Recent fertilizer or pesticide application.
Water source.
Diagnostics
Tests for Toxicity Diagnosis:
Assess blood levels, urine levels, tissue levels, and rumen contents.
Conduct feed/water testing and pasture/environment investigations.
Table 1: Clinical Laboratory Tests Supporting a Toxicologic Diagnosis
Ammonia (serum)
Aplastic anemia
Increase in enzymes: ALP, GGT, AST, ALT, LDH
Azotemia (BUN, creatinine)
Basophilic stippling
Bile acids
Carboxyhemoglobin
Cholinesterase levels
Increase in Creatine Kinase (CK)
Coagulopathy assessment (PT, PTT)
Crystalluria
Hypercalcemia, Hyperkalemia, Hypocalcemia
Nonprotein nitrogen toxicosis, hepatic encephalopathy, excessive protein supplementation
Pathological agents: Bracken fern, phenylbutazone, gasoline
Toxic agents: Aflatoxin, fumonisins, pyrrolizidine alkaloids
Lead poisoning significance (inconsistent in ruminants)
Box 3: Clinical and Necropsy Specimens for Diagnosis
Blood Samples: 5-10 mL in EDTA anticoagulant, stored on ice.
Serum Samples: Centrifuge, remove from clot, store, and submit chilled/frozen.
Brain Samples: Half frozen, half in formalin.
Cerebrospinal Fluid: 2-4 mL submitted in a sterile container.
Rumen and GIT Contents: Collection from various locations; store frozen.
Kidney and Liver Samples: 200 g frozen.
Treatment
Administer activated charcoal (1 g/kg PO ASAP) via oro-ruminal tube.
Perform rumen lavage if necessary using a Kingman tube.
Consider rumenotomy.
Utilize antidotes when available.
Provide supportive care:
IV fluid therapy (IVFT)
Thiamine supplementation
Transfaunation techniques
Antioxidants (e.g., Vitamin E, C)
Change feed/water sources if identified as the source of toxicity.
Consider the health of the rest of the herd.
Toxicants and Related Information
Oleander
Scientific Name: Nerium oleander.
Contains cardiac glycosides (oleandrin and nerine).
Toxicity: 5 leaves toxic for cattle and sheep (green and dried).
Clinical Signs: Sudden death, depression, salivation, weakness, cardiac arrhythmia, diarrhea (D+), mydriasis, and potential hyperkalemia.
Treatment: Anti-arrhythmic drugs; correct potassium levels.
Ionophores
Types include Monensin, Narasin, Salinomycin, Lasalocid.
Clinical Signs: Striated muscle damage, limb weakness/paralysis, observed 1-5 days post-exposure. Symptoms include incoordination, tremors, weakness, tachycardia, hypotension, dyspnea, sweating, recumbency, myoglobinuria.
Monitoring biomarkers: cTnI, CK, AST, ALP, LDH.
Treatment: Anti-arrhythmic drugs; supportive IVFT.
Gossypol
Source: Cottonseed (Gossypium species).
Affected Species: Toxic primarily to monogastrics, though also affects calves, kids, lambs, and swine.
Mechanism: Free radical formation leads to myocardial necrosis, skeletal muscle degeneration, and hepatic changes.
Clinical Signs: 1-2 months after ingestion; symptoms include sudden death, anorexia, cough, dyspnea, brisket edema, ascites, hematuria, thin appearance.
Indicator: Elevated hepatic and muscle enzymes.
Rhododendron/Azalea
Contains Grayanotoxin/Andromedotoxin; all plant parts are toxic.
Most poisonings occur during winter months.
Required Consumption: 0.2% of body weight in leaves to develop clinical signs.
Mechanism: Binds sodium channels, leading to excitation and calcium movement intracellularly, paralleling digitalis toxicity symptoms.
Clinical Signs: Salivation, vomiting (risk of aspiration), hematochezia, weakness, bradycardia, hypotension, atrioventricular (A/V) block, staggering, ataxia, collapse, acute death.
Treatment: Anti-arrhythmic drugs; antibiotics for aspiration.
Perilla Mint
Scientific Name: Perilla frutescens; ketone is a pneumotoxin.
Toxicity Levels: 2.3 kg of seeds or 11.2 kg of hay are lethal to cattle.
Grows in late summer in southeastern U.S. on dry and dormant pastures.
Clinical Signs: Atypical Interstitial Pneumonia (AIP) leading to respiratory distress due to edema and emphysema. Death typically occurs within 3-7 days.
Moldy Sweet Potatoes
Contains the toxin 4-ipomeanol, associated with the fungus Fusarium solani.
Toxin activates into a highly reactive metabolite in the lungs, causing severe pulmonary edema.
Clinical Signs: Tachycardia, tachypnea, dyspnea, loud expiration grunt, frothing at mouth, nostril flare, deep cough. Death can occur 2-5 days post-ingestion.
Histopathology Findings: Damage to club cells, type 1 pneumocytes, proliferation of type 2 pneumocytes, hyaline membrane formation, and edema.
Pyrrolizidine Alkaloids (PAs)
Problems arise from overgrazed pastures or accidental harvesting. Chronic exposure can lead to death within 1-6 months if cattle consume ≥ 5% of their diet.
Young plants are more toxic; lower doses can cause impoverished condition over time.
Clinical Signs: Weight loss, icterus, photosensitization; hepatic encephalopathy can lead to behavioral changes like blindness and aggression.
Diagnosis: Histopathology shows fibrosis, megalocytosis, and bile duct hyperplasia; hepatic and biliary damage evident on chemistry.
Copper
Pathophysiology: Excessive copper (Cu:Mo ratio >10:1) leads to copper accumulation in the liver, resulting in cell necrosis, RBC fragility, hemoglobin oxidation, and methemoglobinemia.
Clinical Signs in Sheep (most sensitive species): Depression, anorexia, weakness, hemolytic crisis, anemia, hemoglobinemia leading to port wine-colored urine, and jaundice.
In cattle, exposure to Copper Disodium Edetate increases dyspnea, head pressing, ataxia, and circling.
Necropsy Findings: Liver appears yellow/friable with extensive necrosis and hepatic fibrosis; kidneys may display a characteristic ‘gunmetal blue’ appearance.
Treatment Options: Ammonium molybdate, sodium thiosulfate, diuretics, blood transfusions, Vitamin E, and molybdenum in feed for other affected animals.
Bracken Fern
Consumption over 1-3 months leads to enzootic hematuria or acute coagulopathy and septicemic crisis due to bone marrow suppression.
Mechanism includes thiaminase production causing Vitamin B1 degradation and ptaquiloside, which is carcinogenic.
Clinical Signs of Thiamine Deficiency: Incoordination, tremors, blindness, and other neurological signs.
Ptaquiloside Effects: Causes hemorrhage, hematuria, and anemia; bladder tumors linked to BPV-2 infections.
Ponderosa Pine
Scientific Name: Pinus ponderosa; associated with isocupressic acid.
Consumed particularly during the last trimester of pregnancy leads to abortion and prematurity due to vasoconstrictive effects on uterine vessels.
Symptoms may include edematous swelling of the udder and vulva prior to abortion.
Lupine
Reproductive Toxicity: Caused by the anagyrine alkaloid during gestation days 40-70 leading to crooked calf syndrome (torticollis, scoliosis, etc.).
Neurotoxicity in Sheep: Due to quinolizidine alkaloid leading to nicotinic effects.
Clinical Signs: Salivation, incoordination, head pressing, aimless wandering, muscle tremors, seizures, and dyspnea.
Nitrate/Nitrite
Sources include various plants and water; influenced by fertilizer application and the environment affecting photosynthesis.
Mechanism: Nitrite ion oxidizes ferrous iron in hemoglobin to the ferric state, forming methemoglobin incapable of oxygen transport.
Symptoms: Present as dark chocolate brown blood, dyspnea, tremors, convulsion, and potential fetal distress.
Treatment: Methylene blue (2-4%) IV at 4-15 mg/kg with minimum 180-day withdrawal after treatment.
Lead
Common sources include batteries, used motor oil, old paint, and machinery grease.
Lead toxicity primarily occurs through GI absorption and can affect multiple systems causing hemolytic anemia and neurological dysfunction.
Clinical Signs: Vary from muscle fasciculations, ataxia, to acute encephalopathy and sudden death.
Diagnosis involves blood testing; chelation therapy with calcium disodium EDTA is the standard treatment.
Thiaminases
Caused by grain overload leading to thiaminase production which leads to thiamine depletion and subsequent PEM (polioencephalomalacia).
Clinical Signs: Include neurological disturbances like blindness, ataxia, seizures, and other significant central nervous system signs.
Treatment Protocol: Thiamine supplementation (20 mg/kg SQ/IM every 4 hours) with the use of steroids being controversial.
Knowledge Check
A case study is examined where a group of yearling steers experiences respiratory distress and seizures after exposure to a neighbor's fertilized pasture. Several specifics include:
Top Differential Diagnosis: Likely nitrate poisoning based on the symptoms observed (chocolate brown blood and mucous membranes).
Antidote Options: Methylene blue or cold water/vinegar to slow nitrification if physiologically appropriate.
Identifying Source: Investigation into recent feeding practices, fertilization details, and possible contaminant plants/water sources.
Questions?
Organophosphates
Known toxicity in large animal species; specific precautions for ruminants, while cattle are less sensitive.
Common Clinical Symptoms: Increased parasympathetic activity resulting in miosis and SLUD signs (Salivation, Lacrimation, Urination, Defecation).