CLINICAL TOXICOLOGY

MUSHROOM POISONING
Presented by:
V.K.Sai Sunaina
IV PharmD
17P91T0029
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Mushrooms

The term mushroom actually refers to reproductive portion of a fungus which grows up from an
underground mycelium, i.e. mass of filaments or hyphae constituting the vegetative portion of the
fungus

Of the numerous species of mushrooms, less than 5% are poisonous, while many are edible and are
very popular in western and Chinese cuisine.

All toxic mushrooms belong to two divisions:

• Basidiomycetes

• Ascomycetes

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Mushrooms
The important parts of a poisonous mushroom include,

• The pileus(cap)-broad cap like structure.

• Stipe(stem or stalk)-stem supporting the pileus

• Lamellae(gills)-spokes of wheel

• Volva(death cup)-remnant of veil

• Veil-membrane that completely or partially covers the lamellae

• Annulus(ring)-ring like structure that surrounds the stipe below its junction with the pileus

• Spores-microscopic reproductive structures that are

produced in millions and range in color from white to black 3

Uses

 Immune system enhancer.

 Source of vitamin D.

 May help protect against cancer.

 May help maintain heart health.

 Used as an anti-oxidant.

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Classification

Depending on the nature of toxin present, mushrooms can be classified into several groups of which
the cyclopeptide containing mushrooms are the most important, and will be discussed here.

Examples include:

Amanita species: A.phalloides,A.virosa, A.bisporigera.

Galerina species: G.autumnalis, G.marginate, G.venenata.

Lepiota species: L.castanea, L.chlorophyllum, L.josserandii.

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Toxins

 Amatoxins, phallotoxins, and virotoxins, which are all cyclopeptides.

 Nine amatoxins have been identified.

 Phallotoxins are bicyclic heptapeptides.

 Seven compounds of phallotoxins have been identified.

 Five virotoxins (monocyclic heptapeptides) have been isolated

from Amanita virosan.

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Mode of Action

Phalloidin - interrupts actin polymerization and impairs cell membrane function, but has a limited
absorption and therefore toxicity.

Phalloidin binds to actin F(filamentous polymer)of the plasma membranes, and hence increases
the permeability of the plasma membranes of hepatocytes.

Amatoxins are more potent and can cause substantial hepatic,renal,and CNS damage.

In vitro studies indicate that alpha-amanitin is cytotoxic on the basis of its interference with RNA
polymerase II, preventing the transcription of DNA.

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Latent Period:

There is often a latent period of 6 to 24 hours following ingestion. The toxins are not destroyed by
cooking.

Clinical(toxic)symptoms:

Phase-I:

• Abdominal pain, nausea vomiting, diarrhea, fever, tachycardia, hypoglycemia, hypotension and
electrolyte imbalance, lasting for about a day.

• Diarrhea is often severe ,watery, and cholera like.

• Metabolic acidosis may occur. 8

Phase-II:

• Treacherous phase of remission, during which the patient may be considered to have recovered and may
even be sent home, only to return in death state soon thereafter.

Phase-III:

• 2 to 3 days after ingestion of toxic mushroom, the third devastating phase unfolds leading to
hepatic,renal,and pancreatic failure.

• Hepatotoxicity manifests in the form of elevations of AST, ALT, and bilirubinlevels,

hypoglycemia,jaundice,encephalopathy with convulsions, coma and death in 7 to 10 days(after ingestion)

• Coagulation defects with hypofibrinogenemia and hypoprothrombinemia occur in hepatic failure, and may
result in local or general bleeding.
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• Hypoglycemia is a grave marker signifying poor prognosis. Spontaneous hypoglycemia results from
impaired glycogenolysis and gluconeogenesis. Insulin and C-peptide concentrations are elevated in
many patients. Amanita toxins appear to be able to induce a direct insulin-releasing effect, and
also have a cytotoxic effect on beta cells. .

• Cardiovascular collapse usually accompanies severe hepatic failure at the terminal stage.

• Adult respiratory distress syndrome(ARDS) may develop in the later stages of cyclopeptide
mushroom poisoning, in conjunction with severe hepatic impairment and coagulopathies.

• Polyneuropathy, developing several days after mush-room ingestion, has been reported in some
patients.
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Usual fatal dose:
• About 2 to 3 mushrooms(A.phalloides).
• Concentration of 5 to 15 mg of amatoxins per gram of dried mushroom have been found, which is
equal to one amanita cap. According to some investigations, 0.1mg/kg of amatoxin may be lethal
dose for human adults.
• About 15 to 20 Galerina caps could kill a healthy adult, as will about 30 Lepiotas

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Diagnosis
 Meixner test-simple colorimetric spot test for the detection of amatoxin.

 Melzer’s test-to detect an amyloid reaction in cyclopeptide containing Amanitas

 Hepatic and renal function tests.

 Serum electrolytes,urea,creatinine,and glucose levels.

 Detection of toxins in liver and kidney biopsies using HPLC,TLC.

 Monitor coagulation parameters(PT),especially clotting factors synthesized by

liver,i.e.fibrinogen,prothrombin.

 Elevated AST, ALT, LDH, and serum bilirubin are the earliest and best indicators of liver damage,
while glucose, fibrinogen, and prothrombin time are the best indica-tors of established
hepatocellular failure. Patients with prothrombin values less than 10% have high fatality rate.
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Treatment
Stabilisation:

• Restoration of fluid and electrolyte balance: vigorous and immediate correction of dehydration and
hypovolaemia.

• IV glucose: Monitor serum glucose levels hourly at the bedside. Give intravenous solutions of 10%
dextrose by continuous infusion, and additional boluses of glucose as indicated by the tests.

• Monitor coagulation tests (prothrombin and fibrinogen) frequently. If hypoprothrombinaemia and

hypofibrinogenemia or clinical haemorrhage is present, give vitamin K (50 to 100 mg/day IV) and
fresh frozen plasma.

• Correction of hypokalaemia (by potassium chloride diluted in solutions of dextrose 5%, or NaCl
0.9%), and of metabolic acidosis (by sodium bicarbonate solution 1.4%) should be guided by
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Treatment
Decontamination:

• Activated charcoal in the usual manner. Multiple dose activated charcoal is recommended by some
the enterohepatic circulation of the amatoxins. Emesis and catharsis are usually unnecessary.

• Toxicokinetic studies indicate that significant amounts of amatoxins are eliminated in urine,
especially during the first 48 hours following ingestion. Forced diuresis (6 to 9 L/day) may therefore
help if the patient is seen within 24 to 48 hours. However it has not been proven to be really
effective.

• Hemoperfusion is said to be beneficial if performed within 24 hours of ingestion. A major risk of

hemoperfusion is thrombocytopenia with increased risk of bleeding.

• Plasma exchange has been tried without conclusive evidence of benefit. Charcoal plasma perfusion
(CPP) and continuous venovenous hemofiltration (CVVH) have been tried successfully in a few14cases.
Treatment
Antidotes:

• Benzyl penicillin at a dose of 300,000 to 1,000,000 units per day is said to be effective in displacing
amatoxin from plasma protein-binding sites allowing for renal excretion.

• Thioctic acid (alpha-lipoic acid) was initially thought to be beneficial in the treatment of hepatic
damage, but subsequent studies have been discouraging.

• Silybinin (an extract of silymarin from the milk thistle Silybum marianum) is being investigated for
its reported beneficial effects in countering hepatotoxicity, but there is no evidence so far of clear-
cut advantage.

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Treatment

• Cimetidine (a potent cytochrome P450 system inhibitor) may have hepatoprotective effects against
alpha- amanitin, and is suggested by some investigators as a therapeutic intervention at a dose of 4
to 6 gm/day.

• N-acetylcysteine (NAC) has been investigated in some patients with various degrees of amanita
poisoning.

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 General Principles
• Hospital admission.
• Invasive monitoring to detect complications before they become clinically evident.
• Placement of CVP monitor, arterial line, urinary catheter, and nasogastric tube.
• Endotracheal intubation if patient is comatose. Continuous pulse oximetry.
• Mechanical ventilation, if there is evidence of hypercapnia or hypoxia.
• Prevention of hypoglycaemia by continuous infusion of 5 or 10% dextrose.
• If hypoglycaemia develops, infuse 50% dextrose.
• Treatment of hypotension with crystalloid or colloid solutions, or drugs such as dopamine,
noradrenalin, etc.
• Treatment of renal failure with dialysis or arterio-venous ultrafiltration.
• Prevention of gastroduodenal bleeding with regular doses of H2 antagonists or omeprazole.
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