Bovis ISSN 2398-2993

Urea toxicity

Synonym(s): Non-protein nitrogen (NPN) poisoning, ammonia toxicosis

Contributor(s): Tiffany Blackett , John Tulloch

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Introduction

  • Cause: poor acclimatization of cattle to feeding urea (NPN - non-protein nitrogen) or the ingestion of excess urea . For example, from poorly mixed feed rations, free access to palatable NPN supplements, and livestock access to ammonium or urea-containing fertilizers.
  • Signs: rapid onset. Muscle tremors, ataxia, dyspnea, bloat, terminal convulsions and death.
  • Diagnosis: history of exposure, clinical effects and clinical pathology, including blood and rumen ammonia levels and rumen pH at time of death.
  • Treatment: supportive care, hydration and the administration of both cold water and acetic acid.
  • Prognosis:  poor without rapid treatment and in severely affected or recumbent animals.

Pathogenesis

Etiology

  • Urea (ie feed grade urea) is a frequently used NPN source in diet supplements in cattle. Other sources of NPN supplements include biuret, and various ammonium salts.
  • Urea is used as a source of NPN for rumen bacterial microbes to make proteins Rumen function and fermentation Rumen microrganisms and microbial protein synthesis
    • During this process the urea is quickly broken down in the rumen and hydrolyzed to ammonia by the rumen microbes’ urease enzymes. 
    • Rumen microbes combine ammonia with products of carbohydrate metabolism to make amino acid and ultimately proteins.
  • It is important that a sufficient amount of digestible carbohydrate is also available as rumen microbes’ conversion of ammonia into proteins is enhanced by high levels of digestible carbohydrate in the diet.
  • However, the rumen microflora must adapt to utilising the higher quantities of ammonia produced from a NPN feed source, such as urea, and this can be achieved by slowly adding NPN or urea to the diet over a period of time and gradually raising the NPN levels in the feed.
  • Acclimatization is also rapidly lost, in 1-3 days, if there is a cessation or temporary interruption of NPN feeding. The animal will be vulnerable to urea toxicity and will need to be reacclimatized before NPN can be fed again.
  • Possible causes of urea toxicity include:
    • Poor acclimatization to feeding NPN.
    • Infrequent feeding of dietary urea.
    • Poor mixing of urea/NPN supplements with feed.
    • Errors in NPN feed supplementation of ration.
    • Excess feeding or ingestion of urea supplements.
    • Free access to urea (NPN) supplements.
    • Freely available palatable liquid supplements containing NPN.
    • Access to and ingestion of ammonium nitrate or urea-containing fertilizers.
    • Access a contaminated water source, for example from urea fertilizers.

Predisposing factors

General

  • Cattle not acclimatized to urea (NPN) feeding.
  • Interruption of NPN feeding.
  • Starvation.
  • Pre-existing debilitation or poor body condition.
  • Dehydration.
  • A low protein diet.
  • A high roughage/high fiber/low energy diet.
  • Lack of digestible carbohydrate in the diet.
  • High rumen pH Rumen pH and the importance of saliva. SARA
  • Increased body temperature.
  • Liver impairment/disease.
  • Concurrent illness.
  • Age - adult cattle.

Pathophysiology

  • The rate of ammonia production in the rumen governs the level of toxicity.
  • Rapid urea hydrolysis by the rumen microflora causes the production of large amounts of ammonia in the rumen, quicker than the microbes can metabolise and convert to proteins, resulting in rapid excess ammonia absorption from the rumen and the subsequent development of toxic effects.
  • Excess ammonia creates an alkaline environment in the rumen. If the rumen pH becomes >7.5, urea hydrolysis is enhanced, resulting in greater ammonia production and increased absorption of ammonia from the rumen. Ammonia absorption is increased when the rumen pH is elevated.
  • Absorbed ammonia is transported to the liver where it is detoxified and converted to urea. Urea is then eliminated in the urine or is recirculated via secretion in the saliva. It is when this hepatic ammonia detoxification pathway becomes exhausted that raised blood ammonia levels (hyperammonemia) occur and signs of toxicity are seen.
  • Systemic ammonia inhibits the citric acid cycle (aka Kreb’s cycle or tricarboxylic acid cycle) causing decreased ATP levels and a lactic acidosis, affecting energy metabolism and causing a hyperkalemia which can result in heart failure.

Timecourse

  • Onset of clinical effects is often rapid, from 10 minutes up to 4 hours post ingestion, depending on the amount ingested.
  • The clinical picture is often acute and clinical progression is rapid once effects are observed. Animals may be found dead.
  • If the animal survives the initial phase, recovery can vary from 8-24 hours, but death can occur 1-4 hours after the onset of effects.
  • There can be a high mortality rate.

Diagnosis

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Treatment

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Prevention

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Outcomes

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Further Reading

Publications

Refereed Papers

  • Recent references from PubMed and VetMedResource.​
  • Shaikat A H, Hasan M M, Hasan S A, Khan S A, Haque M A, Islam M N & Hossain M B (2013) Non-protein nitrogen compound poisoning in cattle. University Journal of Zoology, Rajshahi University 31, 65-68.
  • Antonelli A C, Mori C S, Soares P C, Kitamura S S, Ortolani E L (2012) Acid-base status of ammonia-poisoned steers. Rev Brasil Ciências Agrárias 7(4), 680-683.
  • Antonelli A C, Mori C S, Soares P C, Kitamura S S, Ortolani E (2004) Experimental ammonia poisoning in cattle fed extruded or prilled urea: clinical findings. Braz J Vet Res Anim Sci 41, 67-74.
  • Kitamura S S, Antonelli A C, Maruta C A, Soares P C, Sucupira M C, Mori C S, Mirandola R M & Ortolani E L (2003) A model for ammonia poisoning in cattleVet Hum Toxicol 45(5), 274-277 PubMed.
  • Villar D, Schwartz K J, Carson T L, Kinker J A, Barker J (2003) Acute poisoning of cattle by fertilizer-contaminated water. Vet Hum Toxicol 45(2), 88-90 PubMed.
  • Campagnolo E R, Kasten S, Banerje M (2002) Accidental ammonia exposure to country fair livestock due to contaminated drinking water. Vet Hum Toxicol 44(5), 282-285 PubMed.

Other sources of information

  • Parkes H, Shilton C (2011) Urea Poisoning in cattle. Agnote No. K46.  Northern Territory Government, Australia.
  • Sebastian M M (2007) Feed and food associated toxicosis: NPN (urea/ammonia). In: Veterinary Toxicology, Basic and Clinical principles. Ed Gupta, R C. Elservier Inc. pp1106.
  • Talcott PA. (2007) Nonprotein nitrogen (urea) and hyperammonaemia. In: Veterinary Toxicology, Basic and Clinical principles. Ed Gupta, R C. Elsevier Inc Chapter 84, pp1042-1044.
  • Anon (2006) Urea. In: Veterinary medicine – A textbook of the diseases of cattle, horses, sheep, pigs and goats. 10th Edition. Eds: Radostits OM, Gay CC, Hinchcliff KW, Constable PD. Saunders, Elsevier. Chapter 32: Diseases associated with inorganic and farm chemicals. pp1842-1843.
  • Lieske C and Volmer PA (2004) Non protein nitrogen. In: Clinical Veterinary Toxicology. Ed: Plumlee K H. Mosby. pp130-132.

Organisation(s)

  • Veterinary Poisons Information Service (VPIS), London.  UK.


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