Amanita virosa
Encyclopedia
Amanita virosa, commonly known as the European destroying angel, is a deadly poisonous basidiomycete fungus
Fungus
A fungus is a member of a large group of eukaryotic organisms that includes microorganisms such as yeasts and molds , as well as the more familiar mushrooms. These organisms are classified as a kingdom, Fungi, which is separate from plants, animals, and bacteria...

, one of many in the genus Amanita
Amanita
The genus Amanita contains about 600 species of agarics including some of the most toxic known mushrooms found worldwide. This genus is responsible for approximately 95% of the fatalities resulting from mushroom poisoning, with the death cap accounting for about 50% on its own...

. Occurring in Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...

, A. virosa associates
Mycorrhiza
A mycorrhiza is a symbiotic association between a fungus and the roots of a vascular plant....

 with various deciduous and coniferous trees. The large fruiting bodies (i.e., the mushrooms) appear in summer and autumn; the caps
Pileus (mycology)
The pileus is the technical name for the cap, or cap-like part, of a basidiocarp or ascocarp that supports a spore-bearing surface, the hymenium. The hymenium may consist of lamellae, tubes, or teeth, on the underside of the pileus...

, stipe
Stipe (mycology)
thumb|150px|right|Diagram of a [[basidiomycete]] stipe with an [[annulus |annulus]] and [[volva |volva]]In mycology a stipe refers to the stem or stalk-like feature supporting the cap of a mushroom. Like all tissues of the mushroom other than the hymenium, the stipe is composed of sterile hyphal...

s and gills are all white in colour.

Immature specimens of A. virosa resemble several edible species commonly consumed by humans, increasing the risk of accidental poison
Poison
In the context of biology, poisons are substances that can cause disturbances to organisms, usually by chemical reaction or other activity on the molecular scale, when a sufficient quantity is absorbed by an organism....

ing. Along with its geographical namesakes, A. virosa is one of the most poisonous of all known poisonous mushrooms; its principal toxic constituent α-amanitin
Alpha-amanitin
alpha-Amanitin or α-amanitin is a cyclic peptide of eight amino acids. It is possibly the most deadly of all the amatoxins, toxins found in several species of the Amanita genus of mushrooms, one being the Death cap as well as the Destroying angel, a complex of similar species, principally A....

 damages the liver and kidneys, often fatally. There are only a few known antidotes, one of which is a compound derived from milk thistle
Milk thistle
The milk thistle is a thistle of the genus Silybum Adans., a flowering plant of the daisy family . They are native to the Mediterranean regions of Europe, North Africa and the Middle East...

.

Taxonomy and naming

The common name of destroying angel
Destroying angel
The name destroying angel applies to several similar, closely related species of deadly all-white mushrooms in the genus Amanita. They are Amanita bisporigera and A. ocreata in eastern and western North America, and A. virosa in Europe. Another very similar species, A. verna or fool's mushroom was...

is applied to several all-white species of poisonous Amanita
Amanita
The genus Amanita contains about 600 species of agarics including some of the most toxic known mushrooms found worldwide. This genus is responsible for approximately 95% of the fatalities resulting from mushroom poisoning, with the death cap accounting for about 50% on its own...

, to this species in Europe and to Amanita bisporiga in eastern North America
North America
North America is a continent wholly within the Northern Hemisphere and almost wholly within the Western Hemisphere. It is also considered a northern subcontinent of the Americas...

, and A. ocreata
Amanita ocreata
Amanita ocreata, commonly known as the death angel, destroying angel, angel of death or more precisely Western North American destroying angel, is a deadly poisonous basidiomycete fungus, one of many in the genus Amanita. Occurring in the Pacific Northwest and California floristic provinces of...

in the west. A. virosa was first collected and described by Elias Magnus Fries
Elias Magnus Fries
-External links:*, Authors of fungal names, Mushroom, the Journal of Wild Mushrooming.*...

 in Sweden
Sweden
Sweden , officially the Kingdom of Sweden , is a Nordic country on the Scandinavian Peninsula in Northern Europe. Sweden borders with Norway and Finland and is connected to Denmark by a bridge-tunnel across the Öresund....

. Its specific epithet virosa derived from the Latin
Latin
Latin is an Italic language originally spoken in Latium and Ancient Rome. It, along with most European languages, is a descendant of the ancient Proto-Indo-European language. Although it is considered a dead language, a number of scholars and members of the Christian clergy speak it fluently, and...

 adjective virōsus 'toxic' (compare virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...

).

Amanita virosa is very similar to several other species of all-white amanitas known as destroying angels, which has led to confusion over which occurs where. This specific name has been applied to all-white destroying angels occurring in North America, though others propose these all belong to A. bisporiga and other rarer species instead. There has been some question over whether Amanita verna
Amanita verna
Amanita verna, commonly known as the fool's mushroom, Destroying angel or the mushroom fool, is a deadly poisonous basidiomycete fungus, one of many in the genus Amanita. Occurring in Europe in spring, A. verna associates with various deciduous and coniferous trees...

is a valid species.

Description

A. virosa first appears as a white egg-shaped object covered with a universal veil
Veil (botany)
A veil, in mycology, is one of several structures in fungi, especially the thin membrane that covers the cap and stalk of an immature mushroom.Veils may be regarded as falling into two categories:*Partial veil*Universal veil...

. As it grows, the mushroom breaks free, though there may be ragged patches of veil at the cap edges. The cap
Pileus (mycology)
The pileus is the technical name for the cap, or cap-like part, of a basidiocarp or ascocarp that supports a spore-bearing surface, the hymenium. The hymenium may consist of lamellae, tubes, or teeth, on the underside of the pileus...

 is initially conical with inturned edges, before becoming hemispherical and flattening with a diameter up to 12 cm (4½ in). The cap often has a distinctive boss; it is able to be peeled and white, though the centre may be ivory in colour. The crowded free gills are white, as is the stipe and volva
Volva (mycology)
The volva is a mycological term to describe a cup-like structure at the base of a mushroom that is a remnant of the universal veil. This macrofeature is important in wild mushroom identification due to it being an easily observed, taxonomically significant feature which frequently signifies a...

. The thin stipe
Stipe (mycology)
thumb|150px|right|Diagram of a [[basidiomycete]] stipe with an [[annulus |annulus]] and [[volva |volva]]In mycology a stipe refers to the stem or stalk-like feature supporting the cap of a mushroom. Like all tissues of the mushroom other than the hymenium, the stipe is composed of sterile hyphal...

 is up to 15 cm (6 in) tall, with a hanging grooved ring. The spore print
Spore print
thumb|300px|right|Making a spore print of the mushroom Volvariella volvacea shown in composite: mushroom cap laid on white and dark paper; cap removed after 24 hours showing pinkish-tan spore print...

 is white and the spores egg-shaped conical and 7–10 μm
Micrometre
A micrometer , is by definition 1×10-6 of a meter .In plain English, it means one-millionth of a meter . Its unit symbol in the International System of Units is μm...

 long. They stain blue with iodine
Iodine
Iodine is a chemical element with the symbol I and atomic number 53. The name is pronounced , , or . The name is from the , meaning violet or purple, due to the color of elemental iodine vapor....

. The flesh is white, with a taste reminiscent of radishes, and turns bright yellow with sodium hydroxide.

This fungus highlights the danger of picking immature fungi as it resembles the edible mushrooms Agaricus arvensis
Agaricus arvensis
Agaricus arvensis, commonly known as the Horse Mushroom, is a mushroom of the genus Agaricus.-Taxonomy:Described as Agaricus arvensis by Jacob Christian Schaeffer in 1762, and given numerous binomial descriptions since. Its present name arvensis means 'of the field'.-Description:The cap is similar...

and A. campestris
Agaricus campestris
Agaricus campestris is commonly known as the field mushroom or, in North America, meadow mushroom. It is a widely eaten gilled mushroom closely related to the cultivated button mushroom Agaricus bisporus.-Taxonomy:...

, and the puffballs (Lycoperdon
Lycoperdon
Lycoperdon is a genus of puffball mushrooms. The genus has a widespread distribution and contains about 50 species. In general, it contains the smaller species such as the pear shaped puffball and the gem studded puffball. Most of the time they grow from dead wood and if they grow through the...

spp. ) before the caps have opened and the gills have become visible.

The ability to be peeled has been taken as a sign of edibility in mushrooming, which is a potentially lethal mistake in this species. It is unclear why this fungus which more closely resembles edible species has been implicated in fewer deaths than the death cap
Death cap
Amanita phalloides , commonly known as the death cap, is a deadly poisonous basidiomycete fungus, one of many in the genus Amanita. Widely distributed across Europe, A. phalloides forms ectomycorrhizas with various broadleaved trees. In some cases, death cap has been introduced to new regions with...

, though its rarity may contribute to this.

Distribution and habitat

A. virosa is found in mixed woodland, especially in association with beech
Beech
Beech is a genus of ten species of deciduous trees in the family Fagaceae, native to temperate Europe, Asia and North America.-Habit:...

, on mossy ground in summer and autumn. Most Amanita
Amanita
The genus Amanita contains about 600 species of agarics including some of the most toxic known mushrooms found worldwide. This genus is responsible for approximately 95% of the fatalities resulting from mushroom poisoning, with the death cap accounting for about 50% on its own...

species form ectomycorrhizal
Mycorrhiza
A mycorrhiza is a symbiotic association between a fungus and the roots of a vascular plant....

 relationships with the roots of certain trees.

Toxicity

Amanita virosa is highly toxic, and has been responsible for severe mushroom poisoning
Mushroom poisoning
Mushroom poisoning refers to harmful effects from ingestion of toxic substances present in a mushroom. These symptoms can vary from slight gastrointestinal discomfort to death. The toxins present are secondary metabolites produced in specific biochemical pathways in the fungal cells...

s. Like the closely related death cap (A. phalloides), it contains the highly toxic amatoxin
Amatoxin
Amatoxins are a subgroup of at least eight toxic compounds found in several genera of poisonous mushrooms, most notably Amanita phalloides and several other members of the genus Amanita, as well as some Conocybe, Galerina and Lepiota mushroom species.-Structure:The compounds have a similar...

s, as well as phallotoxin
Phallotoxin
The phallotoxins consist of at least seven compounds, all of which are bicyclic heptapeptides , isolated from the death cap . Phalloidin had been isolated in 1937 by Feodor Lynen, Heinrich Wieland's student and son-in-law, and Ulrich Wieland of the University of Munich...

s. Some authorities strongly advise against putting these fungi in the same basket with those collected for the table and to avoid touching them.

Amatoxins consist of at least eight compounds with a similar structure, that of eight amino-acid rings; they were isolated in 1941 by Heinrich O. Wieland
Heinrich Otto Wieland
Heinrich Otto Wieland was a German chemist. He won the 1927 Nobel Prize in Chemistry for his research into the bile acids. In 1901 Wieland received his doctorate at the University of Munich while studying under Johannes Thiele...

 and Rudolf Hallermayer of the University of Munich
Ludwig Maximilians University of Munich
The Ludwig Maximilian University of Munich , commonly known as the University of Munich or LMU, is a university in Munich, Germany...

. Of the amatoxins, α-amanitin is the chief component and along with β-amanitin is likely responsible for the toxic effects. Their major toxic mechanism is the inhibition of RNA polymerase II
RNA polymerase II
RNA polymerase II is an enzyme found in eukaryotic cells. It catalyzes the transcription of DNA to synthesize precursors of mRNA and most snRNA and microRNA. A 550 kDa complex of 12 subunits, RNAP II is the most studied type of RNA polymerase...

, a vital enzyme in the synthesis of messenger RNA
Messenger RNA
Messenger RNA is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein...

 (mRNA), microRNA, and small nuclear RNA (snRNA). Without mRNA essential protein synthesis
Protein biosynthesis
Protein biosynthesis is the process in which cells build or manufacture proteins. The term is sometimes used to refer only to protein translation but more often it refers to a multi-step process, beginning with amino acid synthesis and transcription of nuclear DNA into messenger RNA, which is then...

 and hence cell metabolism grind to a halt and the cell dies. The liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

 is the principal organ affected, as it is the organ which is first encountered after absorption in the gastrointestinal tract, though other organs, especially the kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...

s, are susceptible.

The phallotoxins consist of at least seven compounds, all of which have seven similar peptide rings. Phalloidin
Phalloidin
Phalloidin is one of a group of toxins from the death cap known as phallotoxins.-Background:Pioneering work on this toxin was done by the Nobel laureate Heinrich Wieland in the 1930s...

 was isolated in 1937 by Feodor Lynen
Feodor Felix Konrad Lynen
Feodor Felix Konrad Lynen was a German biochemist.- Biography :Feodor Lynen was born in Munich, Germany on 6 April 1911. He started his studies at the chemistry department of Munich University in 1930 and graduated in March 1937 under Heinrich Wieland with the work: "On the Toxic Substances in...

, Heinrich Wieland's student and son-in-law, and Ulrich Wieland of the University of Munich. Though phallotoxins are highly toxic to liver cells, they have since been found to have little input into the destroying angel's toxicity as they are not absorbed through the gut. Furthermore, phalloidin is also found in the edible (and sought-after) Blusher (Amanita rubescens). Another group of minor active peptides are the virotoxins, which consist of six similar monocyclic heptapeptides. Like the phallotoxins they do not exert any acute toxicity after ingestion in humans.

Treatment

Consumption of Amanita virosa is a medical emergency
Medical emergency
A medical emergency is an injury or illness that is acute and poses an immediate risk to a person's life or long term health. These emergencies may require assistance from another person, who should ideally be suitably qualified to do so, although some of these emergencies can be dealt with by the...

 requiring hospitalization. There are four main categories of therapy for poisoning: preliminary medical care, supportive measures, specific treatments, and liver transplantation
Liver transplantation
Liver transplantation or hepatic transplantation is the replacement of a diseased liver with a healthy liver allograft. The most commonly used technique is orthotopic transplantation, in which the native liver is removed and replaced by the donor organ in the same anatomic location as the original...

.

Preliminary care consists of gastric decontamination with either activated carbon
Activated carbon
Activated carbon, also called activated charcoal, activated coal or carbo activatus, is a form of carbon that has been processed to make it extremely porous and thus to have a very large surface area available for adsorption or chemical reactions.The word activated in the name is sometimes replaced...

 or gastric lavage
Gastric lavage
Gastric lavage, also commonly called stomach pumping or Gastric irrigation, is the process of cleaning out the contents of the stomach. It has been used for over 200 years as a means of eliminating poisons from the stomach. Such devices are normally used on a person who has ingested a poison or...

. However, due to the delay between ingestion and the first symptoms of poisoning, it is commonplace for patients to arrive for treatment many hours after ingestion, potentially reducing the efficacy of these interventions. Supportive measures are directed towards treating the dehydration which results from fluid loss during the gastrointestinal phase of intoxication and correction of metabolic acidosis
Metabolic acidosis
In medicine, metabolic acidosis is a condition that occurs when the body produces too much acid or when the kidneys are not removing enough acid from the body. If unchecked, metabolic acidosis leads to acidemia, i.e., blood pH is low due to increased production of hydrogen by the body or the...

, hypoglycemia, electrolyte
Electrolyte
In chemistry, an electrolyte is any substance containing free ions that make the substance electrically conductive. The most typical electrolyte is an ionic solution, but molten electrolytes and solid electrolytes are also possible....

 imbalances, and impaired coagulation.

No definitive antidote for amatoxin poisoning is available, but some specific treatments have been shown to improve survivability. High-dose continuous intravenous penicillin G has been reported to be of benefit, though the exact mechanism is unknown, and trials with cephalosporin
Cephalosporin
The cephalosporins are a class of β-lactam antibiotics originally derived from Acremonium, which was previously known as "Cephalosporium".Together with cephamycins they constitute a subgroup of β-lactam antibiotics called cephems.-Medical use:...

s show promise. There is some evidence that intravenous silibinin
Silibinin
Silibinin , also known as silybin, is the major active constituent of silymarin, standardized extract of the milk thistle seeds, containing mixture of flavonolignans consisting of among others of silibinin, isosilibinin, silicristin and silidianin. Silibinin itself is mixture of two diastereomers...

, an extract from the blessed milk thistle (Silybum marianum), may be beneficial in reducing the effects of death cap poisoning. Silibinin prevents the uptake of amatoxins by hepatocyte
Hepatocyte
A hepatocyte is a cell of the main tissue of the liver. Hepatocytes make up 70-80% of the liver's cytoplasmic mass.These cells are involved in:* Protein synthesis* Protein storage* Transformation of carbohydrates...

s, thereby protecting undamaged hepatic tissue; it also stimulates DNA-dependent RNA polymerases, leading to an increase in RNA synthesis. N-acetylcysteine has shown promise in combination with other therapies. Animal studies indicate the amatoxins deplete hepatic glutathione
Glutathione
Glutathione is a tripeptide that contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side-chain...

; N-acetylcysteine serves as a glutathione precursor and may therefore prevent reduced glutathione levels and subsequent liver damage. None of the antidotes used have undergone prospective, randomized clinical trials, and only anecdotal support is available. Silibinin and N-acetylcysteine appear to be the therapies with the most potential benefit. Repeated doses of activated carbon may be helpful by absorbing any toxins that are returned to the gastrointestinal tract following enterohepatic circulation
Enterohepatic circulation
Enterohepatic circulation refers to the circulation of biliary acids from the liver, where they are produced and secreted in the bile, to the small intestine, where it aids in digestion of fats and other substances, back to the liver....

. Other methods of enhancing the elimination of the toxins have been trialed; techniques such as hemodialysis
Hemodialysis
In medicine, hemodialysis is a method for removing waste products such as creatinine and urea, as well as free water from the blood when the kidneys are in renal failure. Hemodialysis is one of three renal replacement therapies .Hemodialysis can be an outpatient or inpatient therapy...

, hemoperfusion
Hemoperfusion
Hemoperfusion is a medical process used to remove toxic substances from a patient's blood. The technique involves passing large volumes of blood over an adsorbent substance. The adsorbent substance most commonly used in hemoperfusion are resins and activated carbon...

, plasmapheresis
Plasmapheresis
Plasmapheresis is the removal, treatment, and return of blood plasma from blood circulation. It is thus an extracorporeal therapy...

, and peritoneal dialysis
Peritoneal dialysis
Peritoneal dialysis is a treatment for patients with severe chronic kidney disease. The process uses the patient's peritoneum in the abdomen as a membrane across which fluids and dissolved substances are exchanged from the blood...

 have occasionally yielded success but overall do not appear to improve outcome.

In patients developing liver failure, a liver transplant is often the only option to prevent death. Liver transplants have become a well-established option in amatoxin poisoning. This is a complicated issue, however, as transplants themselves may have significant complications
Complication (medicine)
Complication, in medicine, is an unfavorable evolution of a disease, a health condition or a medical treatment. The disease can become worse in its severity or show a higher number of signs, symptoms or new pathological changes, become widespread throughout the body or affect other organ systems. A...

 and mortality; patients require long-term immunosuppression
Immunosuppression
Immunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other...

 to maintain the transplant. That being the case, there has been a reassessment of criteria such as onset of symptoms, prothrombin time
Prothrombin time
The prothrombin time and its derived measures of prothrombin ratio and international normalized ratio are measures of the extrinsic pathway of coagulation. This test is also called "ProTime INR" and "INR PT". They are used to determine the clotting tendency of blood, in the measure of warfarin...

 (PTT), serum bilirubin
Bilirubin
Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...

, and presence of encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy is the occurrence of confusion, altered level of consciousness and coma as a result of liver failure. In the advanced stages it is called hepatic coma or coma hepaticum...

 for determining at what point a transplant becomes necessary for survival. Evidence suggests that, although survival rates have improved with modern medical treatment, in patients with moderate to severe poisoning up to half of those who did recover suffered permanent liver damage. However, a follow-up study has shown that most survivors recover completely without any sequelae if treated within 36 hours of mushroom ingestion.

See also

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