mushroom and marine lnl greller - acmt.net · 8/20/14! 1! m & m! mushrooms and marine! howard...
TRANSCRIPT
8/20/14!
1!
M & M!Mushrooms and Marine!
Howard A. Greller MD FACEP FACMT!
Introduction!• Mushrooms are the fruiting body of a fungus!
• More than 40,000 species worldwide!
• 5000 species in U.S., < 2% poisonous!
• 79% poison < 6 years old!
• Raw >> cooked!
• Allergy and anaphylaxis more common than poisoning!
8/20/14!
2!
Mushroom Anatomy!and identification!
cup (volva)
(mycelial threads)
(lamella)
(annulus)
(pileus)
(stape)
Cap
Ring
Gills
Spores
Stalk Hyphae
Mushroom ID!• Books!
• Location!
• Size, color, shape!
• Spore print!
• Spore ID!
• Mycologist!
8/20/14!
3!
http://namyco.org/!
Tricksy mushrooms!yeeesssss. . . precious . . .!
8/20/14!
4!
Yes, horsey?!
pssst. . . Nicholas . . .!eat these. they’re yummy.!
There are old mushroom hunters, and there are bold mushroom
hunters. But there are no old, bold mushroom hunters.!
8/20/14!
5!
Mushroom Taxonomy!Classification!
Cyclopeptides!Group I!
Amanita phalloides! Amanita verosa!
8/20/14!
6!
Amanita species - cyclopeptides!- A. phalloides (death cap), A. virosa (death angel)!
- 95% mushroom related fatalities, 50% case fatality!- One mushroom enough to kill an adult!
Galerina autumnalis! Lepiota helveola!
Galerina & Lepiota species - cyclopeptides!- G. autumnalis, G. marginata, G. venenata!- L. helveola, L. josserandi, Lbrunneoincarnata!
8/20/14!
7!
Cyclopeptides!Amatoxins (cyclic octapeptides)!
- heat stabile!
- interferes with RNA polymerase II, protein translation!- sodium-taurocholate co-transporter polypeptide!- centrilobular hepatic necrosis with intact architecture!
- α-amanitin !
- poorly absorbed, enterohepatic recirculation!
Cyclopeptides!Phallotoxins (cyclic heptapeptides)!- Phalloidin!- limited absorption!- interrupts actin polymerization!- impairs cell membrane function!
8/20/14!
8!
Cyclopeptides!Virotoxins (cyclic heptapeptides)!- Virotoxin!- ? human toxicity!
Toxicity - cyclopeptides!Phase I!- not earlier than 6 hours, lasts up to 24 hours!- initial cholera-like diarrhea, then nausea/vomiting!Phase II!
Phase III!
- “quiescent” phase (no n&v)!- hepatotoxicity!
- hepatic, renal, pancreatic!- death 2-3 days after ingestion!
8/20/14!
9!
Therapeutics - cyclopeptides!Early!- volume resuscitation!- ? MDAC!- ? hemodialysis / hemoperfusion!Late(r)!- thioctic (α-lipoic) acid!- penicillin G (1.6 million U/kg/day)!- silymarin (silibinin) from milk thistle!- n-acetylcysteine!- cimetidine!
Therapeutics!
• Bioartificial liver!
• Liver transplant!
• Early >> late!
8/20/14!
10!
Gyrometrin!Group II!
gyromitra esculenta! morchella esculenta!
8/20/14!
11!
Gyromitra species - gyromitrin!
- found in spring under conifers!- G. esculenta, G. californica, G. brunnea, G. infula!
- often confused for the edible morel!
Gyromitrin!- N-methyl-N-formyl hydrazone!
- heat sensitive (although fumes have ? toxicity)!- hydrolyzed to monomethylhydrazine !
gyromitrin! monomethylhydrazine!
➜➜➜!
Toxicity - gyromitrin!- asymptomatic for at least 6 hours!
- seizures!- initial GI symptoms!
8/20/14!
12!
glutamic acid! GABA!GAD!
pyridoxine!
pyridoxal 5’ phosphate!
PPK!hydrazines!
8/20/14!
13!
Therapeutics - gyromitrin!Early!- ? GI decontamination!Seizures!- benzodiazepines!- pyridoxine (vit B6)!
- 70 mg/kg up to 5 grams!- anesthetic barbiturates!
pyridoxine!
Muscarine!Group III!
8/20/14!
14!
clitocybe clavipes! inocybe geophylia!
Clitocybe species - muscarine!- C. dealbata (‘the sweater’),C. illudens!
Inocybe species - muscarine!- I. Iacera, I. geophylla!
8/20/14!
15!
Muscarine!Quarternary ammonium compound!
- Not nicotinic!- Does not cross BBB (no CNS) !
- Not susceptible to ACHase hydrolysis!
acetylcholine! muscarine!
Toxicity - muscarine!- Rapid onset of toxicity (within 30 minutes)!
- NO nicotinic findings (i.e. mydriasis, tachycardia, weak)!- SLUDGE!
8/20/14!
16!
Therapeutics - muscarine!- Atropine (infrequently required)!
- NO oximes (i.e. 2-PAM)!
- ACLS doses to start!- titrate until relief of symptoms, dry secretions!
8/20/14!
17!
Coprine!Group IV!
Coprinus atramentarius! Coprinus comatus!
Coprinus - coprine!- C. comatus, C. atramentarius!- Undergo “autodigestion” - inky caps!- pleasant tasting, edible mushrooms!
- problematic with ethanol (disulfiram like reaction)!
8/20/14!
18!
Coprine!Toxicity comes from primary metabolite!- 1-aminocyclopropanol!
coprine! 1-aminocyclopropanol!
- ethanol present or ingested within 24-48 hours!
➜➜➜!
- usually okay if done together (delayed toxicity)!
Toxicity - coprine!- rapid onset of toxicity (within 1 hour)!
- flushing!- disulfiram reaction!
- nausea & vomiting!- tachycardia!- headache!
- inhibits aldehyde dehydrogenase!
disulfiram!
8/20/14!
19!
Therapeutics - coprine!- intravenous fluids!- antiemetics!- analgesics!- time (for ethanol to be metabolized)!
+! =!
Ibotenic acid / Muscimol!Group V!
8/20/14!
20!
Amanita muscaria! Amanita gemmata!
Amanita muscaria - ibotenic acid / muscimol!- A. muscaria (fly agaric), A. pantherina, A. gemmata!- popular children’s books and games!
- Babar, Super Mario Bros.!
NOT MUSCARINIC, NOT ANTI MUSCARINIC!
Ibotenic acid / muscimol!
- structurally similar to glutamic acid!
- decarboxylated metabolite of ibotenic acid!
Ibotenic acid!
Muscimol!
- similar to GABA!
ibotenic acid! muscimol!
glutamic acid! GABA!
8/20/14!
21!
Toxicity - ibotenic acid / musicmol!
- ibotenic acid stimulates glutamic acid receptors!
- rapid onset (0.5 - 2 hours), resolves 6-12 hours!
- musicmol acts as a GABA agonist!
- mild GI upset!
- somnolence, ataxia!
- hallucinosis, excitation!
- seizures rare (GABAB agonism)!- adults manifest more GABA-ergic symptoms!- pediatrics excitatory transmission predominates!
Therapeutics - ibotenic acid / muscimol!- supportive care!- benzodiazepines for seizures, excitation!- no role for flumazenil for sedation!
8/20/14!
22!
Falling in love is like eating (poisonous) mushrooms.!
!You never know if it is the real thing
until it’s too late.!
Psilocybin / Psilocin!Group VI!
8/20/14!
23!
Psilocybe cubensis! Psilocybe cyanescens!
Psilocybe species - psilocybin / psilocin!- P. cyanescens, P. cubensis, G. spectabilis, P. foenisecii!- “magic mushrooms”!
- Native american religious customs, drug culture!- when handled, develop blue bruises!
Psilocybin / psilocin!Structural similarity to serotonin!
- rapid onset, medium duration (1 - 6 hours)!- interact with serotonin receptors, no adrenergic effects!
psilocybin! serotonin! psilocin!
- psilocybin is rapidly hydrolyzed to psilocin!
8/20/14!
24!
illusion! hallucination!
pallinopsia! synesthesia!
Toxicity - psilocybin / psilocin!- Early GI effects (0.5 - 1 hour)!- illusions!- synesthesias!- “heightened perceptions”!
- true hallucinations are rare and dose dependent!- autonomic response to altered perceptions!
8/20/14!
25!
Therapeutics - psilocybin / psilocin!Primary supportive care!- benzodiazepines!- avoid neuroleptics!
- risk hallucinogen persistent perceptive disorder (HPPD)!
Little Brown Mushrooms!Group VII!
8/20/14!
26!
russula emetica! Chlorophyllum molybdites!
Little Brown Mushrooms (LBM) - GI toxins!- Boletes, Lactarius sp., Omphalotus sp., Tricholoma sp.!- Lycoperdon sp., Agaricus, Entoloma, Chlorophyllum sp.!
- Often mistaken for edible or hallucinogenic!- Largest group of mushrooms!
LBM - GI toxins!Heterogenous toxins!
- unknown specific mechanism or toxin!- terpenes and lactones!
- direct irritant? allergic phenomenon?!
8/20/14!
27!
Toxicity - LBM!- Early GI effects (0.5 - 3 hours)!- rapid resolution without significant consequence!- Paxillus Syndrome (rare)!
- P. involutus, Clitocybe claviceps, Boletus luridus!- involutin? (diphenylcyclopenteneone)!- immune-mediated hemolytic anemia, renal failure!- repeated long term exposure!
Therapeutics - LBM!Primary supportive care!- intravenous hydration!- antiemetics!- antidiarrheals!Prevention!
8/20/14!
28!
Orelline / Orellanine!Group VIII!
cortinarius speciosissimus! cortinarius archeri!
Cortinarius sp. - orelline / orellanine!- C. orellanus, C. speciosissimus, C.rainierensis (NA)!- Only recent recognition of toxicity!
8/20/14!
29!
Oreline / Orellanine!Bipyridyl agents!
- heat stable!- similar to paraquat/diquat!
- direct irritant? allergic phenomenon?!
orellanine! paraquat!
Toxicity - orelline / orellanine!- asymptomatic for 24 - 26 hours!- headache, chills, anorexia, n/v (flu-like)!- oliguric renal failure!
- ATN!- similar prognosis to other causes of ATN!
Therapeutics - orelline / orellanine!Primary supportive care!- intravenous hydration!- hemodialysis!- transplantation reported, but very rare!Prevention!
8/20/14!
30!
Allenic norleucine!Group IX!
amanita smithiana! tricholoma magnivelare!
8/20/14!
31!
Amanita smithiana - allenic norleucine!- mistaken for tricholoma magnivelare (matsutake)!- Pacific N.W. US!
Allenic norleucine!2-amino-4,5-hexadienoic acid!
- may be the compound !- limited mechanistic information!
Toxicity - allenic norleucine!
- early GI distress (0.5 - 12 hours)!- malaise, diaphoresis, dizzy!
- 4-6 days after ingestion!- acute renal failure!
- ALT, LDH elevated !
Phase I!
Phase II!
- renal tubular toxin!
8/20/14!
32!
Therapeutics - allenic norleucine!Primary supportive care!- no known antidote!- ? AC!- consider hemodialysis given location/history, etc.!Prevention!
Myotoxin!Group X!
8/20/14!
33!
tricholoma equestre! tricholoma flavovirens!
Tricholoma equestre - myotoxin!- T. flavovirens!- “man on horseback” (Fr), “yellow knight” (US)!
Toxicity - myotoxin!
- delayed symptoms 24-72 hours after ingestion!- fatigue, myalgia, weakness!
- nausea, diaphoresis, facial erythema!- CPK elevations and rhabdomyolysis!
- biopsy shows acute myopathy!- acute myocarditis, dysrhythmias, CHF possible!
- unknown what the toxin is!
- mortality as high as 25%!- therapy is supportive!
8/20/14!
34!
N Engl J Med 2001;345!
mushroom philosophy!• Color, odor, taste, location DO NOT predict
toxicity!
• Symptoms NOT always from mushroom toxin!
• pesticides, allergies, other (i.e. sauce)!
• Early symptoms good, late symptoms bad!
• exception Group IX allenic norleucine!
• not always just one type of mushroom!
8/20/14!
35!
wrap up!• Identifiable early symptoms (< 6 hours)!
• Supportive care!
• Delayed onset of symptoms!
• MDAC!
• Admission!
• More aggressive therapy?!
All mushrooms are edible . . . once.!
8/20/14!
36!
OVERVIEW!
CIGUATERA!
8/20/14!
37!
Ciguatera!- endemic to warm waters, bottom reef dwellers!
- more than 500 species!- large fish (more than 4 lbs)!
- > 50k cases in U.S./year!- Hawaii & Florida > 90% of cases!
- viscera and gonads!
Parrot Fish! Sea Bass!
35 degrees north to 35 degrees south!
from May through August!
8/20/14!
38!
Amberjack! Red Snapper!
Ciguatoxin!- bioaccumulated & concentrated dinoflagellates!
- gambierdiscus toxicus!- heat stable, lipid soluble!- odorless, tasteless, colorless!
Grouper!
8/20/14!
39!
SYMPTOMS!• diaphoresis, chills!
• abdominal pain!
• nausea / vomiting / diarrhea!
• dysuria !
• painful defecation / ejaculation!
• temperature reversal!
• dental pain (“loose”)!
• paresthesias!
• lingual, perioral, extremity!
• arthralgia, myalgias!
• vertigo, ataxia!
VOLTAGE SENSITIVE SODIUM CHANNEL!
CONCERNING SYMPTOMS!
• t-wave abnormalities!
• bradycardia!
• hypotension!
• pulmonary edema!
• respiratory paralysis !
• coma!
8/20/14!
40!
Toxicity - ciguatoxin!- most prominent symptoms are neurologic!
- dysesthesias (i.e. hot/cold reversal)!- “dental pain” (i.e. tooth are loose or “itch)!
- small percentage with bradycardia / hypotension!
- Bagnis, Am J Trop Med Hyg, 1979!
Barracuda!
Ciguatoxin!- symptoms 2-6 hours after eating!
- GI and diaphoresis!- more than 75% within 12 hours!
- neurologic symptoms between 2 and 24 hours!
- There is an ELISA assay!
8/20/14!
41!
Sturgeon!
Therapeutics - ciguatoxin!- GI decon (self)!
- Symptomatic therapy!- consider AC!
- antihistamines!- atropine for bradycardia!
- Mannitol!- unknown mechanism, ? reverse neuro ?!- early >> late!- 1 g/kg of 20% solution over 30min / 2-6 hr!- theories!
8/20/14!
42!
Yellowfin Tuna!
Scombroid!- temperate or tropical waters!- non-scombroidae (most common)!
- scombroidae!- skipjack, tuna, mackerel!
- mahi mahi, amberjack!
- first described cases!
8/20/14!
43!
Scombroid - histamine!
- histidine decarboxylated to histamine!
histidine! histamine!
histidine!decarboxylase!
- heat stable!
- improper refrigeration (> 20℃ / 68℉)!- bacteria on fish skin!
- peppery tasting!- “honeycomb” appearance rare!
Symptoms - scombroid!- within 5 to 90 minutes!
- n/v/d, dizziness, palps, hypotension!
- lasts 12-24 hours untreated!
- rarely puritis, urticaria, angioedema!
- flushing (face, neck, torso)!
- bronchospasm, visual loss!
8/20/14!
44!
Mahi-Mahi!
Differential - scombroid!- Allergic reaction!- MSG reaction!- Disulfiram reaction!
- Carcinoid!- Zollinger-Ellison syndrome!
- Tyramine reaction!
8/20/14!
45!
Therapeutics - scombroid!- Supportive!- H1 / H2 blockers!- Serious reactions!
- Reassurance and education!- bronchodilators, epi, etc!
diphenhydramine!
TETRODOTOXIN!
fugu! hapalochlaena maculosa!
8/20/14!
46!
Tetrodotoxin!- puffer fish and blue-ringed octopus!
- fresh and saltwater!
- octopus is small (< 5”) and non-aggressive!- venom expressed by beak!
- puffer fish skin and gut make toxin!- frogs, horseshoe crabs/eggs, salamanders!
Toxicity - tetrodotoxin!- highest concentrations in liver and ovary!
- female more toxic than male!- blocks voltage-gated Na channels!
- blocks axonal neurotransmission!- PNS, CNS, autonomic, cardiac!
8/20/14!
47!
Symptoms - tetrodotoxin!- GI within 3 hours!
- n/v/d, abd pain!- Neurologic minutes to hours!
- Ascending paralysis, respiratory depression!
- Death reported within 17 minutes!!
- progressive parasthesias!- progressive weakness (bulbar), ataxia!
- Survival beyond 24 hours excellent prognosis!
- Preserved mental status!
JAPANESE 4 STAGES!
• Oral paresthesias, ? GI!
• Advanced paresthesias, ext paralysis, + DTR!
• Gross incoordination, aphonia, dysphagia, resp distress, hypotension, fully conscious!
• Mental impairment, resp paralysis, ↓BP!
8/20/14!
48!
Differential Dx - tetrodotoxin!- Botulism!
- Progressive supranuclear palsy (PSP)!- Guillan-Barré!
- Ciguatera!
FUGU WA KUITASHII, INOCHI WA OSHISHII!
Therapeutics - tetrodotoxin!- aggressive supportive care!
- no specific laboratory study!- diagnostic testing to exclude other causes!
- admission, observation!
8/20/14!
49!
SHELLFISH POISONING!
Shellfish poisoning!
- paralytic shellfish poisoning!
- amnestic shellfish poisoning!
- dinophysis or prorocentrum!
- neurotoxic shellfish poisoning!
- “diarrhetic” shellfish poisoning!
- dinoflagellate or algae contamination!
- protogonyaulax catanella & tamarensis!
- ptychodiscus brevis (gymnodinium breve)!
- nitzschia pungens!
8/20/14!
50!
Paralytic Shellfish Poisoning!
Toxicity - saxitoxin!- blocks voltage-sensitive Na channel!
- similar to tetrodotoxin!
saxitoxin! s.aks-itoxin!
8/20/14!
51!
Symptoms - saxitoxin!- neurologic (within 30 min)!
- paresthesias, numbness, “floating”, HA, vertigo!
- GI symptoms less common!
- ataxia, muscular weakness!- dysphagia, dysarthria, dysphonia, blindness!- paralysis!
- weakness can last weeks!
- supportive!Therapeutics - saxitoxin!
Neurotoxic Shellfish Poisoning!
8/20/14!
52!
Toxicity - brevetoxin!- stimulates voltage-sensitive Na channel!
- similar to ciguatera!
brevetoxin!
ciguatera!
Symptoms - brevetoxin!
- neurologic!
- vertigo, ataxia, tremor!
- GI symptoms!
- dysphagia, bradycardia, ⬇ DTRs, mydriasis!- NO paralysis!
- n/v/d, abd pain, rectal burning!
- paresthesias, “hot/cold reversal”, myalgias, HA!
- GI with neuro symptoms simultaneously!- incubation ≈ 3 hr (15 min - 18 hr)!- duration ≈ 17 hr (1 - 72 hr)!
8/20/14!
53!
Amnestic Shellfish Poisoning!
Toxicity - domoic acid!- glutamate agonist!
- analog of glutamic and kainic acids!
domoic acid! kainic acid!
- AMPA & kainate receptor damage ➜ Ca influx!
8/20/14!
54!
Symptoms - domoic acid!
- neurologic!- memory loss (10% long term anterograde)!
- GI symptoms less common!- seizures, hemiparesis!- ophthalmoplegia!- chewing/grimacing!
- onset within 5 hr (15 min - 36 hr)!
- carries mortality of ~ 2% (older)!
8/20/14!
55!
Diarrhetic Shellfish Poisoning!
Toxicity - okadoic acid!- phosphatase a1 & a2 inhibitor!
- phosphorylates proteins control Na secretion!
okadoic acid!
- permeability of intestinal cell membranes!- degeneration of absorptive epithelium!
8/20/14!
56!
Symptoms - okadoic acid!- GI symptoms (30 min - 2 hours)!
- n/v/d, abd pain!- self limited (2 - 3 days)!
- supportive!Therapeutics - okadoic acid!
Questions?!