Title 19. PLANTS POISONING - MUSHROOMS, MYCOTOXINS.pdf ✅

PHARMD GURU Page 1 MUSHROOM POISONING INTRODUCTION:  The term “mushroom” actually refers to the 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 and Ascomycetes.  The important parts of a poisonous mushroom (careful examination of which can help in identification) include the pileus (cap), stipe (stem or stalk), lamellae (gills), volva, veil, annulus (ring), and spores.  Pileus refers to the broad, cap-like structure from the undersurface of which hang the gills or lamellae. The latter radiate out like the spokes of a wheel. PLANTS POISONING: MUSHROOMS, MYCOTOXINS. PARTS OF A MUSHROOM
PHARMD GURU Page 2  Spores are located on the lamellae, and are microscopic reproductive structures which are produced in the millions and range in colour from white to black, with shades of pink, brown, and purple in between. Stipe is the stalk or stem supporting the pileus.  The annulus (“ring of death”) is a ring-like structure that surrounds the stipe below its junction with the pileus.  The veil is a membrane that completely or partially covers the lamellae.  Volva (“death cup”) represents the remnant of the veil found around the base of the stipe in some species.  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 comprising A. phalloides, A. virosa, A. bisporigera, A. hygroscopica, A. suballiacea, A. tenuifolia, A. verna, and A. ocreata  Galerina species comprising G. autumnalis, G. marginata, G. sulcipes, and G. venenata.  Lepiota species comprising L. castanea, L. helveola, L. chlorophyllum, L. josserandii, L. subincarnata, and L. brunneoincarnata. TOXINS:  Amatoxins, phallotoxins, and virotoxins, which are all cyclopeptides.  Nine amatoxins have been identified: alpha, beta, gamma, and epsilon amanitins, amanullin, amanullinic acid, proamanullin and amanin.  Amanitins are the most toxic compounds. Phallotoxins are bicyclic heptapeptides.  Seven compounds have been identified: phalloidin, phalloin, prophalloin, phallisin, phallacin, phallacidin, and phallisacin. Five virotoxins (monocyclic heptapeptides) have been isolated from Amanita virosa. MODE OF ACTION:  Mushrooms belonging to this group have no characteristic taste or smell.  The colour varies with the climate, soil, and age of the mushroom.
PHARMD GURU Page 3  Identification is based on the presence of white gills underneath the cap, an annulus at the top of the stalk, and a volva at its base.  Specimens cut off at ground level may be misidentified. The swollen base is seen only when the entire fruiting body is dug out of the ground.  Of all the toxins, phalloidin appears to be the most rapid acting, while amanitin causes more delayed manifestations.  Phalloidin interrupts actin polymerisation and impairs cell membrane function, but has a limited absorption and therefore toxicity.  Phalloidin binds to the 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.  Target organs are those with the highest rate of cell turnover—GI tract epithelium, liver hepatocytes, and kidneys.  Cells with the highest rate of multiplication, such as the intestinal mucosa, are injured first, followed by the liver and kidneys. LATENT PERIOD: There is often a latent period of 6 to 24 hours following ingestion. The toxins are not destroyed by cooking. CLINICAL FEATURES: 1. PHASE I: a) Abdominal pain, nausea, vomiting, diarrhoea fever, tachycardia, hypoglycaemia, hypotension and electrolyte imbalance, lasting for about a day. The diarrhoea is often severe, watery, and cholera-like (up to 2 to 4 litres/day). b) Metabolic acidosis may occur.
PHARMD GURU Page 4 2. 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 moribund soon thereafter. 3. PHASE III: a) Two to three days after ingestion of the toxic mushroom, the third devastating phase unfolds leading to hepatic, renal, and (occasionally) pancreatic failure. Hepatotoxicity manifests in the form of elevations of AST, ALT, and bilirubin levels, hypoglycaemia, jaundice, encephalopathy with convulsions, coma, and death in 7 to 10 days (after ingestion). In most cases, encephalopathy occurs 5 to 7 days after ingestion. Coagulation defects with hypofibrinogenaemia and hypoprothrombinaemia occur in hepatic failure, and may result in local or general bleeding. Fulminant hepatic failure, developing very quickly, and requiring liver transplantation has been reported following severe intoxications. Lactic acidosis and metabolic acidosis have also been reported in the 3rd phase. b) Hypoglycaemia is a grave marker signifying poor prognosis. Spontaneous hypoglycaemia 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. Some investigators suggest that aminotransferases are important biological markers, and advocate that monitoring transaminases and measuring their ratio may be of prognostic value. But the general consensus is that prothrombin time is a more useful prognostic marker for clinical outcome than serum aminotransferase levels, although close monitoring of both are recommended. c) Cardiovascular collapse usually accompanies severe hepatic failure at the terminal stage. Sequelae which may follow include cardiomyopathy, coagulopathy, and seizures. When liver damage is reversible, patients usually make a slow and steady recovery. d) Adult respiratory distress syndrome (ARDS) may develop in the later stages of cyclopeptide mushroom poisoning, in conjunction with severe hepatic impairment and coagulopathies. ARDS resulting in death has been reported.