Heavy metals Flashcards
Discuss risk assessment of iron overdose
Potentially lethal
Risk assessment is based on the ingested dose of elemental iron
Refinement of initial assessment can be achieved by
-AXR
-4-6 hour level
Patient who are symptomatic on arrival have poor prognosis and may not respond to medical treatment
Elemental iron dose <20mg/kg -asymptomatic 20-60mg/kg - GIT symptoms 60-120mg/kg - Systemic toxicity anticpitated >120mg/kg potenitally lethal
Discuss toxic mechanisms of iron
Local
- direct corrosive effect on the GI mucosa manifests with symptoms ranging from vomiting and diarrhoea to haematemesis and melaena
- Large GI loss may contribute to significant hypovolaemia
- Systemic toxicity does not occur in the absence of GI symptoms
Systemic
- Iron acts a direct cellular toxin via poorly understood mechanisms
- Chief targets are the CVS and liver
- CNS toxicity is secondary to CVS insitability and metabolic derangement
- Severe metabolic acidosis is observed following large overdoses and attributed to lactic acid formation and the liberation of hydrogen ions form the hydration of free ferric ions in the plasma
- Coagulopathy is frequently observed and attributed to interference with the coag cascaade
Discuss toxicokinetics of iron overdose
Absorption of iron from the GIT is normaly finely regulated according to the needs of the body
- In overdose these mechanisms are overwhelmed and the bioavailability of iron increases significantly
- Absorbed iron shifts intracellularly over a period of hours
- elimination is minimal under normal conditions
Discuss clinical features
Classically has 5 stage Stage 1: 0-6 hours (GI phase) -direct corrisve effect on the GIT -vomiting diarrhoea abdominal pain -fluid loss may be sufficient to cause hypovolaemic shock
Stage 2: 6-12 hours (quiescent/latent)
- Progressive increase in iron absorption and distribution
- some resolution of symptoms may be observed giving false hope of recovery
Stage 3 12-48 hours (cardiogenic shock and acidosis)
- Disruption of cellular metabolism
- manifest as shock from vasodilation and third spacing +GI loss
- HAGMA
- Hepatorenal failure
Stage 4 2-5 days (hepatic necrosis)
- Acute hepatic failure with jaundice,coma and hypoglycaemia, coagulopathy and elevated aminotransferases
- This phase is rare but has high mortality
Stage 5 2-6 weeks (bowel obstruction
- Delayed sequalae
- Cirrhotic liver
- GI fibrosis and strictures leading to obsturction
Discuss IX iron overdose
ECG, BGL paracetamol
Serum iron consentration
- usually a peak at 4-6 hours
- clear correlation between iron levels and clinical toxicity has not been made
- however peak levels >90 mic/l are thought to be predicitve of systemic toxicity
ABG
-HAGMA is a useful marker of systemic toxicity
AXR
-useful in confirming ingestion and planning and monitoring decontamination
Discuss management of iron overdose
Resus
- early priority is the restoration of adequate circulating volume
- give boluses of 10-20ml/kg
- ongoing replacement is often necessary due to GI loss and third spacing
- end points of UO and lactate mentition
Decontaminaion
- iron is not adsorbed by activeated charcoal
- Whole bowel irrigation is the decontamination mehtod of choice and recommened for ingestions >60mg/kg confiremed on XR
Enchanced elimination not used
Antidotes
-Desferrioxamine chelation therapy is indicated if systmeic toxicity is present or predicted by serum iron level >90mic/L at 4-6 hours post ingestion - defrerrioxamine binds free iron makes a water soluble inert chelate that is excreted in urine
Discuss disposition of iron overdose
Children who ahve ingested less than <40mg/kg can be followed up at home
- Larger or symptomatic ingestions are evaluated in hospital
- children who remain asymptomatic at 6 hours and have a -ve AXR can be discharged
- All adults with deliberate self poisoning with iron are evaluated in hopsital
Discuss Arsenic risk assessment
Acute ingestion is usually int he context of deliberate self poisoning.
Acute or subacute ingestion of inorganic arsenic leads to a dose dependenat sequential pattern of MOF
- INgestion of>1mg/kg is potentially lethal
- ingestion of <0.05mg/kg may cause mild self limiting GIT symptoms but does not cause systmeic toxicity
Chornic arsenic intoxication usually occurs secondary to long term (>10 eyars) drinking contaminated artesian water.
Children any ingestion shoud be regarded as potentially lethal
DIscuss TM and TK of arsenic
TM: binds to numerus cellular enymes interferes with cellular respiration and inhibits DNA replication and repair. It binds to sulfhydral groups and substitues for phosphate in ATP - produces reactive o2 intermediates causing lipid peroxication
TK:
Absorption occurs via dermal resp and GI routes. Elimination half life is 3-5 days following acute ingestion. Aresenic intially distributes to kidney and liver. Following chornic ingestion it dsitributes to liver, kidneys, lungs nervous system spleen hair and nails Undergoes hepatic methylation and the metabolitses are excreted in the urine.
Discuss clinical features of aresnic toxicity
Acute
- following large ingestion there is rapid onset of severe watery diarrhoea vomiting and abdominal pain
-Gi haemorrahge can occur
-encephalopathy siezures and CVS collapse can develop within hours
Hypersalivation and garlic odour are characteristic
-Acute cardiomyopathy, ECG changes and cardiac dysrythmias have been described
- ARDS, renal failure and hepatic injury follow
-Bone marrow depression develops wihtin 24-72 hours in survivors reaching nadir in 2-3 weeks
-peripheral neuropathy may develop with a delay of 1-3 weeks. It is ascending predominantly motor neuroapthy and may mimic GBS
Subacute
- initially manifest with GIT symptoms +lecuopenia + deranged LFT and haematuria
- Peripheral neuropathy devlops after sevarl weeks
Chronic toxicity
-insidious onset over years of multisystem disorder manifested by constitutional symptoms, cutaneous lesions, nail changes, painful peripheral neuropathy (glove and stocking)
Discuss IX of arsenic poisoning
ECG, paracetaml, BGL
Spot urine arsenic (nomral <30mic or 400nmol/l)
- helpful to confirm ingestion
- levels after acute infgestion may be >1000mic
24 hour arsenic excretion
-better reflection of body burden
Blood levels
-limied utility
FBC, coags, LFTs, U*E, ABG
CXR and AXR inorganic arsenic compounds are radioopaque
*patients should be advised to aviod eating seafood or seaweed for 3-4 days prior to urine arsenic tets
Discuss management of arsenic poisoning
REsus:
ABCD
immediate life threat in early arsenic poisoning is hyopvolaemia and shock secondary to profound GIT fluid loss
D: ACtivated charcoal does not bind aresenic
- Co-operatiev patient undergo whole bowle irrigation with polyethylene glycol
E: nil
A: CHelation is indicated where there are objective clinical finding or where subacute intoxication is diagnosed on the bases of history of exposure clinical features and elveated urinary arsenic concentration
-Succimer is the agent of choice where oral administration is avialable
-Dimercaprol should be administered by IM where oral is not feasable due to GI syptoms
Discuss risk assessment of lead
Acute or subacute severe lead intoxication occurs in the context of ingestion or inhalational occupational exposures, It is associated with encephalopathy, cerebal oedema and death.
Chronic occupational or environmental exposure usually leads to a vague multisystem disorder with the potential for permanent neurological and neuropsych sequalae. ‘
Pregnancy - major malformation are reported in children born to mothers with elevated lead levels
CHILDREN: exposure to lead is neurotoxic and associated with impaired intellectual development. There appears to be no threshold below which lead is not deleterious during early development.
Lead blood level
<10 - minor reduction in IQ
10-30 - subtle development learning, motor and intellectual abnormalities in children
30-100 - Non specific constituiional symptoms, such as abdo pain, malaise headache htn and insomina. Subclinical impariment of PNS conduction, over peripheral neuropathies
> 100 severe GIT symptoms, encephalopathy, seizure coma and death
Discuss TM and TK of lead
TM: nil physiological function. It has toxic effects through interference with intracellular functions
TK: Absorption via oral, topical and inhaled routes. Absorption from lead foreign bodies such as shotgun pellets lodged in joints or other body cavities also occurs
Oral absorption in children is greater than adults (50% and 20% bioavailable respectively)
Lead is abosrbed and bound be RBC then distributed widely through the body. THe bony skeleton acts as a major lead store. Other sites of deposition include the CNS kidney and spleen. Bone stores can remobilise for decades after exposures has ceased resulting in persistently high levels for months to years. Lead easily crosses the placenta and significant foetal transfer can occur.
Discuss clinical features of lead intoxication
ACUTE
- Abdo pain, nausea vomiting and haemolytic anaemia and hepatitis.
- Cerebral oedema, encephaloapthy, seizures and coma are pre-terminal events
- clinical effects correlate with levels although there is a wide interindividual variation
CHRONIC
- Vague constitutional symtpoms and multi-system effects include impaired concentration, anorexia, vague abdominal pain, emotional lability, weight loss, arthralgia and impaired co-ordination
- Subclinical impairment of higher centre function including IQ
