AFIP Wednesday Slide Conference - No. 21
February 24, 1999

Conference Moderator:
COL Michael J. Langford
Division of Pathology
Walter Reed Army Institute of Research
Washington, DC 20307-5100
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Case I - H98-0948 (AFIP 2641252)

Signalment: Ten-month-old, Hereford steer.
History: Steers in a commercial feedlot were fed a diet to which sodium molybdate had been accidentally added (instead of sodium bicarbonate) at a rate of 1.9% of the total ration. Affected animals were inappetent and weak. Of the 800 steers in the consignment, 90 died.
Gross Pathology: There were widespread subcutaneous petechial hemorrhages. The liver was pale tan, with irregular, focal, 3-5 mm diameter hemorrhages on both the capsular and cut surface. The kidneys were swollen and pale.
Laboratory Results: In a euthanized animal that had access to the contaminated feed for up to 6 days, the plasma molybdenum concentrations were 13,000 mg/L (430 times the normal level). Kidney molybdenum concentrations were 21mg/kg (15 times the normal level), and liver molybdenum concentrations were 12 mg/kg (12 times the normal levels). Fungal cultures of feed samples were negative.
Contributor's Diagnoses and Comments:
1. Liver: Necrosis, acute, diffuse, severe with mild neutrophilic cholangitis and pericholangitis.
2. Kidney: Tubular necrosis, acute, moderate.

Etiology: Molybdenum toxicity.
The contaminated diet in this outbreak contained 7400 mg of molybdenum per kilogram of feed. The rapid rise in plasma molybdenum concentrations suggest that in cattle, as in humans, molybdenum absorption is passive and non-saturable. Tissue molybdenum levels had returned to normal concentrations within 70 days of the contaminated feed being withdrawn. Previous reports of molybdenosis in cattle have involved dietary concentrations of molybdenum between 20 and 200 mg/kg, and symptoms were consistent with a molybdenum-induced copper deficiency.
The gross and histopathological changes seen were suggestive of a fungal or plant toxin. The hepatic lesions of periacinar to massive necrosis accompanied by hemorrhage were suggestive of toxicity by blue-green algae (Nodularia spumigena or Microcystis aeruginosa), zamia palm (Macrozamia reidlei) or by Myoporum insulare ("boobialla"), a plant known to grow in the area. Examination of water from troughs, dams and holding tanks showed no evidence of blue-green algae, and cattle had no access to trees or shrubs. Hepato-renal lesions have been described with toxicity associated with the ingestion of Lantana sp., or with plants containing polyphenols or tannins, such as yellow wood (Terminalia oblongata), black wattle (Acacia salicina) and supplejack (Ventilago viminalis).
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Case 21-1. Kidney. There is pyknosis and karyorrhexis of tubular epithelial cells (necrosis). Other tubular epithelial cells are hyperchromatic with large open nuclei (suggests regeneration). There is a mild interstitial lymphocytic infiltrate.
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Case 21-1. Liver. Bile ducts contain neutrophils and are surrounded by edema. There is degeneration and necrosis of adjacent hepatocytes.
AFIP Diagnoses:
1. Kidney: Necrosis and regeneration, tubular, diffuse, with granular and hyaline casts, Hereford, bovine.
2. Kidney: Nephritis, interstitial, lymphoplasmacytic, multifocal, mild.
3. Liver: Necrosis, disseminated.
4. Liver: Cholangiohepatitis, neutrophilic, diffuse, mild.
Conference Note: Participants identified extensive, sometimes submassive, hepatic necrosis and neutrophilic portal inflammation that multifocally filled bile ducts and disrupted the limiting plate. Viable hepatocytes were present among individually dissociated and necrotic hepatocytes. In addition to necrosis of the tubular epithelium in the kidney, tubular regeneration and casts were observed.
Molybdenum is an essential trace element in plants, humans, and ruminants. The metal is necessary for plants to fix nitrogen, while in animals it serves as a cofactor in the enzymes xanthine oxidase, aldehyde oxidase, and sulfite oxidase. Within the body, molybdenum is concentrated in the liver, kidneys, bones, pancreas, adrenal glands, and omentum. Molybdenum elimination occurs primarily through the renal system, with over 50% of excreted molybdenum found in the urine; some is excreted through perspiration in humans.
While the lesions in the steer represent acute molybdenum toxicosis, the vast majority of reported cases are due to chronic toxicity primarily associated with ingestion of green pasture plants grown on soils high in molybdenum, such as muck or shale soils in Florida, California, and the western United States ("teart" soils in England). Ruminants are most commonly affected, especially cattle. Clinical signs and pathological findings reflect disorders of the integumentary, musculoskeletal, reproductive, hematolymphatic, and gastrointestinal systems. Clinical signs include emaciation, lethargy, rough hair coat, malodorous diarrhea, pale mucous membranes (due to anemia), sterility, and reluctance to move or pain upon locomotion. Pathological findings include microcytic hypochromic anemia, enlargement of long bone epiphyses and costochondral articulations in young animals, rarefaction of bone and fractures in older animals, and increased developmental anomalies in neonates born to affected animals. Permanent aspermatogenesis occurs in bulls, and while reversible ovarian dysfunction may be present in cows.
Contributor: Agriculture Western Australia, Division of Veterinary and Biomedical Sciences, Murdoch University, South Street, Murdoch, Western Australia 6150.
1. Swan DA, et al.: Molybdenum poisoning in feedlot cattle. Aust Vet J 76:345-349, 1998.
2. Jones TC, Hunt RD, King NW: Diseases due to extraneous poisons. In: Veterinary Pathology, 6th ed., page 736, Williams and Wilkins, Baltimore, MD, 1997.
3. Goyer RA: Toxic effect of metals. In: Casarett and Doull's Toxicology: The Basic Science of Poisons, Klaassen CD, ed., 5th edition, page 718, McGraw-Hill, New York, 1996.

Case II - 97-3319 (AFIP 2648171)

Signalment: Five-month-old, male, Ile de France, ovine.
History: Several animals out of a group of 200 Ile de France sheep reared in the Mpumalanga Province (north-eastern region) of South Africa developed nervous symptoms. Affected sheep initially displayed an unsteady and stiff gait which progressed over the course of a few days to total spasticity, convulsions and lateral recumbency with paddling, followed by death. Sheep of both sexes and all ages were affected, though signs were not noted in sheep younger than five months. The sheep had been grazing for several months on kikuyu pastures in the mornings and paddocks of Phalaris grass and another unspecified grass type in the afternoons. The specific Phalaris cultivar was not identified, as the owner did not wish to incur further expenses. The sheep were regularly drenched with anthelmintics and had been inoculated with a multivalent Clostridium/Pasteurella vaccine. A live, five-month-old ram exhibiting a stiff gait and periodic convulsions was presented for necropsy.
Case 21-2. Gross Images (The lesions described below are very subtle in these photos.)
Gross Pathology: The most striking lesions were diffuse brown discoloration of the cerebral and cerebellar gray matter, thalamus, brain stem and medulla; dark brown renal cortices; and diffuse olive green to bluish discoloration of the renal medullae. Incidental lesions included mild hydrothorax and hydropericardium, and low numbers of wire-, nodular-, and tapeworms were present. After formalin fixation, scattered multifocal dark brown to black specks, probably representing pigmented nuclei, were evident in the brain stem and medulla.

Laboratory Results: Liver and kidney copper values were within normal limits.
Contributor's Diagnosis and Comments: Brain stem/medulla: Neuronal cytoplasmic lipofuscin pigmentation, multifocal, moderate.
A section of medulla or brain stem is submitted for examination. Scattered pigmented neurons, usually involving specific nuclei, are evident. Affected neurons are either mildly swollen or slightly shrunken and basophilic. The pigment is present loosely dispersed perinuclearly as golden or dark brown pigment granules, or more commonly in a distinct clump to the one side of the nucleus. The granules were strongly positive for lipofuscin with the Schmorls' stain, but negative for hemosiderin (Prussian blue stain). Mild widening of the perineuronal and perivascular spaces, probably attributable to edema, is evident. Isolated glial cells in the neuropil between affected neurons reveal nuclear pyknosis. Other lesions (tissues not submitted) included moderate pigmentation of the ventral spinal motor neurons, mild status spongiosis of the spinal cord white matter, mild multifocal pigmentation of renal cortical and medullary epithelial cells, and scattered renal medullary lipofuscin casts.
Neuronal lipofuscinosis has been described in sheep in South Africa in outbreaks of Phalaris staggers and Trachyandra divericata poisoning, and in individual aged sheep.1,5 The case presented is typical for the chronic form of Phalaris poisoning referred to as Phalaris staggers. Phalaris poisoning in sheep is reported to occur in three forms: a "sudden death" syndrome; acute Phalaris poisoning associated with transient nervous signs; and a chronic form referred to as Phalaris staggers.1 Bourke et al. proposed that Phalaris poisoning presents as two syndromes: an acute syndrome (the so-called "sudden death" syndrome) characterized by sudden development of neurological signs in the absence of microscopic changes in the central nervous system (CNS); and a chronic syndrome (i.e. Phalaris staggers) characterized by gradual development of neurological signs and the presence of characteristic lesions in the CNS.4 The latter form is a slowly progressive, irreversible, neurological disorder which occurs in sheep several weeks to months after grazing on Phalaris pastures.1,4 The nervous signs are thought to be due to 3-tryptamine alkaloids which are structurally similar to serotonin.1 No reference could be found as to the relationship between these alkaloids and the development and accumulation of the lipofuscin-type pigment.
The "sudden death syndrome" was previously believed to be due to sudden cardiac arrest, but recent evidence suggests that it can occur as one of two presentations: a cardiac presentation or polioencephalomalacic (PEM) presentation. At least four different underlying mechanisms are thought to be responsible for this syndrome: cardio-respiratory toxins (possibly phenylethylamines and some related chemical structures); a thiaminase; cyanogenic compounds; and nitrate compounds. The cardiac presentation occurs uncommonly and is characterized by cardiac arrhythmias and tachycardia followed by ventricular fibrillation. The PEM form is characterized histologically by typical lesions of thiaminase-associated PEM.
Phalaris poisoning is a well-known condition in Australia and New Zealand where it has been attributed mainly to the perennial grass Phalaris aquatica and, to a lesser extent, the annual grass P. minor. In South Africa, only sporadic outbreaks have been reported in the Western Cape attributable to P. minor.1,2 The present outbreak is the only one that has been reported outside the Western Cape.
The principal differential diagnosis for neuronal pigmentation of sheep in southern Africa includes old age pigmentation in individual aged sheep (reportedly not evident in sheep <3 years)5 and poisoning due to the ingestion of tumble-weed (Trachyandra laxa and T. divaricata). In the latter condition, pigmentation is only rarely evident grossly as occasional khaki-brown flecks in scattered nuclei of the brain stem and/or in the spinal cord gray matter. Definitive differentiation between Phalaris staggers and Trachyandra poisoning rests on pasture/veld investigation for the presence of Phalaris or Trachyandra plants.
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Case 21-2. Brainstem. Neurons contain granular brown perinuclear pigment.
AFIP Diagnosis: Brain stem, neurons: Brown granular pigmentation, perinuclear, multifocal, moderate, Ile de France, ovine.
Conference Note: Phalaris and Trachyandra sp. plants are known to induce intense lipofuscin storage in neurons of the thalamus, spinal cord, and peripheral ganglia, although the toxic principle and pathogenesis remain to be identified. While the observation of the pigment in neurons is diagnostically useful in suspected cases of toxicity, especially in young animals, the accumulation of lipofuscin does not seem sufficient to explain the clinical signs and mortality. As noted by the contributor, some authors have proposed that central nervous system signs result from serotonergic effects of toxins on upper motor neurons. The presence of lipofuscin may represent accumulation of indolic metabolites in neuronal lysosomes.
Other conditions causing excessive accumulation of lipopigments within neurons discussed by conference participants included Gomen disease of horses and inherited ceroid-lipofuscinosis. Gomen disease occurs in horses in New Caledonia, and a toxin is suspected as the underlying etiology. Gomen disease is characterized by cerebellar neuronal degeneration, loss of Purkinje and granule cells, thinning of the molecular layer, and accumulation of lipofuscin in surviving Purkinje cells and neurons of the brain and spinal cord. Inherited ceroid-lipofuscinosis is due to an autosomal recessive trait reported in sheep, cattle, dogs, and cats. Neurons at all levels of the brain and spinal cord contain lipopigments, and many other cell types are frequently affected as well.
Contributor: Onderstepoort Veterinary Institute, Pathology Section, PO Box 12502, Onderstepoort 0110, South Africa.
1. Kellerman TS, Coetzer JAW, Naudé TW: Plant poisonings and mycotoxicoses of livestock in southern Africa, 2nd ed., pp. 24-28, Oxford University Press, Cape Town, South Africa, (in print).
2. Van Halderen A, Green JR, Schneider DJ: An outbreak of suspected Phalaris staggers in sheep in the Western Cape Province. J South African Vet Assoc 61:39-40, 1990.
3. Bourke CA, Carrigan MJ: Mechanisms underlying Phalaris aquatica "sudden death" syndrome in sheep. Australian Vet J 69:165-167, 1992.
4. Bourke CA, Carrigan MJ, Seaman JT, Evers JV: Delayed development of clinical signs in sheep affected by Phalaris aquatica staggers. Australian Vet J 69:31-32, 1987.
5. Newsholme SJ, Schneider DJ, Reid C: A suspected lipofuscin storage disease of sheep associated with ingestion of the plant, Trachyandra divaricata. Onderstepoort J Vet Res 52:87-92, 1985.
6. Jubb KVF, Huxtable CR: The nervous system. In: Pathology of Domestic Animals, Jubb KVF, Kennedy PC, Palmer N, eds., 4th edition, vol. 1, pp. 285 and 317-321, Academic Press, San Diego, CA, 1993.
7. Summers BA, Cummings JF, de Lahunta A: Degenerative diseases of the central nervous system. In: Veterinary Neuropathology, page 263, Mosby Yearbook, St. Louis, MO, 1995.
8. Jolly RD, Walkley SU: Lysosomal storage diseases of animals: An essay in comparative pathology. Vet Pathol 34:527-548, 1997.

Case III - 98-1263 (AFIP 2638861)

Signalment: Sixteen-month-old, female, Dorset sheep.
History: The ewe was noted to be off feed in the morning and was dead when checked again in the early afternoon of the same day. No previous signs were noted.
Gross Pathology: The ewe was moderately obese. Petechiae were seen on the visceral pleura lining the thoracic cavity and paralleling the coronary vessels. The liver was firm and had an accentuated lobular pattern.
Laboratory Results: The liver copper level was 333 mg/g (toxic range is greater than 250 mg/g), and the kidney copper level was 149 mg/g (toxic range is greater than 18 mg/g).
Contributor's Diagnoses and Comments:
1. Hepatocellular necrosis, centrilobular, severe, acute, liver.
2. Periportal fibrosis, biliary hyperplasia, and occasional megalocytosis, liver.
The liver has severe, nearly massive, centrilobular and midzonal hepatocellular necrosis together with severe periportal to bridging fibrosis and biliary hyperplasia. Approximately 10-15% of the hepatocytes remain. In addition to necrosis, most centrilobular regions have severe hemorrhage. Some hepatocytes that remain in periportal zones are large and have big, vesicular nuclei (karyomegaly). There is fibrosis and biliary hyperplasia that bridges portal areas. Fibrosis breaches the limiting plates and extends into hepatic lobules. The periportal zones have mild to moderate sized accumulations of macrophages admixed with a few lymphocytes. Many of the macrophages have pale, brown cytoplasmic pigment.
Intratubular hemoglobin casts were observed in the kidney in addition to the hepatic changes. The acute hepatocellular necrosis, taken with the kidney lesions, suggests acute hemolytic crisis precipitated by copper intoxication. This is supported by the elevated liver and kidney copper levels. The periportal fibrosis, biliary hyperplasia, and megalocytosis suggest an underlying pyrrolizidine alkaloid toxicosis or aflatoxicosis. Pyrrolizidine alkaloids are the most significant hepatotoxins associated with chronic copper poisoning, with Heliotropium or Echium sp. being the most common. Pyrrolizidine alkaloid inhibition of hepatocyte mitosis, which decreases the ability of the liver to replace hepatocytes lysed by excessive copper, is one possible mechanism.
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Case 21-3. Liver. There is diffuse centrilobular to submassive hepatocellular necrosis.
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Case 21-3. Liver. There is proliferation of periportal fibroblasts and bile duct epithelial cells, with adjacent necrotic hepatocytes.
AFIP Diagnoses:
1. Liver: Necrosis, centrilobular to submassive, with hemorrhage and intrahistiocytic light greenish-brown pigment, Dorset sheep, ovine.
2. Liver: Biliary hyperplasia and bridging portal fibrosis, diffuse, mild to moderate.
Comment: Some participants observed intranuclear inclusions which were considered to be non-viral. Participants identified biliary hyperplasia and bridging portal fibrosis, but did not identify hepatocyte megalocytosis. The rhodanine stain performed at the AFIP revealed moderate amounts of intracytoplasmic copper within Kupffer cells in portal areas and small amounts within periportal hepatocytes.
Conference Note: Copper is unique among the heavy metals for its selective toxic effects on the liver. Of the domestic animal species, sheep are the most prone to copper poisoning. The avidity of the liver for copper, coupled with the limited rate of copper excretion in the bile in sheep, predispose these animals to chronic copper toxicity. Additionally, chronic copper poisoning in sheep is related to three environmental factors: excessive copper intake, such as from contaminated pasture; increased bioavailability of dietary copper due to low molybdenum levels resulting in excessive absorption and accumulation (molybdenum forms insoluble complexes with copper in the gastrointestinal tract); and the presence of other hepatotoxins, such as pyrrolizidine alkaloids, predisposing animals to outbreaks.
In the absence of contributory factors, liver copper concentrations less than 200-300 parts per million (ppm) on a dry matter basis seem to cause little hepatocellular damage in sheep. Microscopic changes occur in the liver at levels of 300 ppm or more, observed initially as single cell hepatocyte apoptosis and neutrophilic inflammation. The apoptotic rate increases as the level of copper accumulation increases, and the mitotic rate simultaneously increases to keep pace with lost hepatocytes. Sheep with liver concentrations in excess of 1,000 ppm may be clinically and hematologically normal, if the mitotic rate produces adequate numbers of new hepatocytes to take up copper released by dying liver cells. When hepatocellular loss exceeds the rate of replacement, copper spills into the plasma in high enough concentrations to damage erythrocytes, causing intravascular hemolysis, which further accelerates hepatocellular necrosis. Thus, hepatocellular mitotic activity is critical to the delay of acute hemolytic crises.
Pyrrolizidine alkaloids, found in a variety of toxic plants, are well-known for their antimitotic effect on hepatocytes. The interference of hepatocellular replication leads to acute hemolytic crisis at an earlier stage of copper accumulation in affected sheep. This mechanism probably explains the marginal elevation in liver copper levels of the clinically affected sheep submitted for examination. Less specific stresses, such as brief periods of starvation, may also precipitate a hemolytic crisis. Histologically, pyrrolizidine alkaloid hepatotoxicity is characterized by hepatocyte megalocytosis, with concurrent biliary hyperplasia and portal fibrosis. The severity of portal fibrosis is species variable, being minimal to mild in sheep, moderate in horses, and severe in cattle, in which veno-occlusive disease may be observed.
Conference participants did not initially attribute the microscopic lesions in the liver of this sheep to chronic copper toxicosis and pyrrolizidine alkaloid exposure. Megalocytosis is a consistent microscopic feature in cases of pyrrolizidine alkaloid toxicosis, and participants did not consider this a prominent finding in the examined sections. Biliary hyperplasia and portal fibrosis are relatively nonspecific changes. Chronic hepatic disease of various causes may secondarily lead to abnormal accumulation of copper in the liver. Thus, participants found it difficult to determine the pathogenesis of the liver lesions and accumulation of copper. After learning of the laboratory and other pathologic findings, participants agreed with the contributor's assessment of this case.
Contributor: Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040.
1. Howell JH, et al.: Experimental copper and Heliotrope intoxication in sheep: Morphological changes. J Comp Pathol 105:49-74, 1991.
2. Seaman JT: Hepatogenous chronic copper poisoning in sheep associated with grazing Echium plantagineum. Australian Vet J 62:247-248, 1985.
3. Seaman JT: Pyrrolizidine alkaloid poisoning of sheep in New South Wales. Australian Vet J 64:164-167, 1987.
4. Jones TC, Hunt RD, King NW: Diseases due to extraneous poisons. In: Veterinary Pathology, 6th ed., pp. 708 & 712-718, Williams and Wilkins, Baltimore, MD, 1997.
5. Jones TC, Hunt RD, King NW: The digestive system. In: Veterinary Pathology, 6th ed., pp. 1098-1100, Williams and Wilkins, Baltimore, MD, 1997.
6. Kelly WR: The liver and biliary system. In: Pathology of Domestic Animals, Jubb KVF, Kennedy PC, Palmer N, eds., 4th edition, volume 2, pp. 392-400, Academic Press, San Diego, CA, 1993.

Case IV - ND1 (AFIP 2641844)

Signalment: Three-month-old Hereford heifer.
History: Several calves tore down a fence around a lagoon overflow pond. A total of three calves were found dead near the lagoon. A heavy algal growth was noted on the lagoon surface.
Gross Pathology: Per the referring veterinarian, petechiation of serosal surfaces of abdominal organs was present. Only the liver was submitted to the diagnostic laboratory. On cut surface, coalescing areas of hemorrhage were noted throughout the hepatic parenchyma.
Laboratory Results: A water sample from the lagoon submitted to the North Dakota Department of Health identified pure growth of Microcystis aeruginosa.

Contributor's Diagnosis and Comments: Liver: Centrilobular necrosis and hemorrhage, severe, acute, coalescing with centrilobular hepatocellular disassociation.

Etiology: Toxicosis due to Microcystis aeruginosa ("blue-green algae") and microcystin-LR toxin.
Microcystin-LR, a hepatotoxin produced by the blue-green algae Microcystis aeruginosa, sporadically causes sudden death in livestock. Typical case histories indicate lagoons or ponds with a heavy algal bloom that is ingested by drinking livestock. The ultrastructural lesion, occurring as early as ten minutes after ingestion, is a rearrangement of the actin cytoskeleton leading to cell rounding, disassociation, and degeneration. Necrosis of hepatocytes is observed at 60 minutes. Light microscopic changes include centrilobular necrosis and hemorrhage, as seen in this case. Differential diagnosis included bovine pestivirus (bovine viral diarrhea), Clostridium chauvoei, salmonellosis, lead toxicosis, and lightning strike.
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Case 21-4. Liver. There is degeneration, individualization, and necrosis of hepatocytes throughout the lobule with centrilobular hemorrhage and hemosiderin deposition.
AFIP Diagnosis: Liver: Necrosis, massive, with hepatocellular disassociation and hemorrhage, Hereford, bovine.
Conference Note: Several species of blue-green are known to cause poisoning in domestic and wild animals or birds in various parts of the world. Most documented cases involved Microcystis aeruginosa, though other species known to cause toxicity include members of the genera Anabaena, Oscillatoria, and Nostoc. While outbreaks of blue-green algae poisoning are uncommon, they can be responsible for high mortality. The algal blooms have been associated with water runoff from fertilized soil, and the algae may then become concentrated on the shoreline of ponds due to the effects of wind. Poisoning occurs most commonly in ruminants, although cases have also been reported in horses, dogs, sheep, swine, and domestic poultry.
In most poisoned animals, death occurs within hours of ingestion of contaminated water, and few animals recover. A few cases may have a subacute or chronic clinical course. When observed, clinical signs in acute cases include prostration followed by convulsions, or generalized paralysis. Generalized petechiation and cavitary effusions are observed at necropsy in acute cases. In subacute and chronic cases, clinical signs reflect hepatic insult and include ataxia, depression, anorexia, hemorrhagic diarrhea, and icterus. Necropsy findings in subacute cases include icterus and a fatty, yellow, friable liver. In chronic cases, the liver may be hard and cirrhotic; severe cutaneous lesions caused by photosensitization may be observed in recovered animals.
Freshwater blue-green algae produce a variety of hepatotoxins known as microcystins that are inhibitors of protein phosphatases. The toxic principle, microcystin-LR, is released upon disintegration of algae either in the water, or within the rumen or stomach after ingestion. Microcystin-LR is one of the most potent hepatotoxins and produces coagulative necrosis and hemorrhage in the liver. Covalent binding of protein phosphatases by microcystin-LR inhibits the activity of the enzymes and leads to hyperphosphorylation of cytoskeletal proteins, rearrangement of intermediate filaments and microtubules, and disorganization of the cytoskeleton, resulting in disassociation and necrosis of hepatocytes. Microcystin-LR also causes necrosis of endothelial cells in the liver and may result in embolization of hepatocytes to the lung. Recently, some investigators have attributed the extensive coagulative necrosis in the liver to ischemia based upon the distribution of the microscopic lesions in the early stages of experimentally induced toxicity in rodents. Both mechanisms probably contribute to the severity of the hepatic lesion. Microcystins also have tumor promoting activity in animals.
Contributor: North Dakota State University, Veterinary Diagnostic Laboratory, Fargo, ND 58105.
1. Hooser SB, et al.: Microcystis-LR-induced ultrastructural changes in rats. Vet Pathol 27:9-15, 1990.
2. Hooser SB, et al.: Actin filament alternatives in rat hepatocytes induced in vivo and in vitro by microcystin-LR, a hepatotoxin from the blue-green alga, Microcystis aeruginosa. Vet Pathol 28:259-266, 1991.
3. George LW: Diseases of the nervous system. In: Large Animal Internal Medicine: Diseases of Horses, Cattle, Sheep, and Goats, Smith BP, ed., 2nd edition, pp. 1078-1080, Mosby-Year Book, St. Louis, MO, 1996.
4. Kelly WR: The liver and biliary system. In: Pathology of Domestic Animals, Jubb KVF, Kennedy PC, Palmer N, eds., 4th edition, volume 2, pp. 385-386, Academic Press, San Diego, CA, 1993.
5. Jones TC, Hunt RD, King NW: Diseases due to extraneous poisons. In: Veterinary Pathology, 6th ed., pp. 723-724, Williams and Wilkins, Baltimore, MD, 1997.
6. Yoshida T, et al.: Immunohistochemical localization of microcystin-LR in the liver of mice: A study on the pathogenesis of microcystin-LR-induced hepatotoxicity. Toxicol Pathol 26:411-418, 1998.
Ed Stevens, DVM
Captain, United States Army
Registry of Veterinary Pathology*
Department of Veterinary Pathology
Armed Forces Institute of Pathology
(202)782-2615; DSN: 662-2615
* The American Veterinary Medical Association and the American College of Veterinary Pathologists are co-sponsors of the Registry of Veterinary Pathology. The C.L. Davis Foundation also provides substantial support for the Registry.
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