Toxicity of the Lithium Ion

1
Toxicity of the Lithium Ion

• Robyn Fullerton
• Environmental Sciences Program
• Southern Illinois University Edwardsville
• ENVS531

2
Outline

• I. Introduction/Background
• II. Toxicity
• III. Mechanism of Toxicity
• IV. Treatments
• V. Current Status

3
Introduction/Background

• Compounds addressed
• lithium aluminum hydride
• lithium chloride
• lithium carbonate
• Sources of lithium
• minerals
• spodumene
• petalite
• lake brines

4
Introduction/Background

• Common uses of lithium
• manufacturing
• ceramics and glass
• batteries
• 80 of lithium consumed
• pharmaceuticals
• major source of lithium toxicity
• 13 of lithium consumed
• treatment for acute mania and bipolar disorder

5
Toxicity

• Acute (single-exposure)
• typically mild
• occurs when absorptive peak reached in patient
• effects
• gastrointestinal disturbances
• vomiting, nausea, diarrhea, abdominal pain
• neurological disturbances
• fine tremors
• sedation
• mimics sodium deficiency

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Toxicity

• Acute (continuous intake)
• occurs after build-up of lithium from a
  week/month of continuous intake
• effects
• gastrointestinal disturbances
• profuse diarrhea and vomiting
• cardiovascular system
• arrhythmias, hypotension, and pulmonary edema

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Toxicity

• Acute (continuous intake)
• effects, cont.
• neurological disturbances
• delirium, hyperreflexia, seizures, coma and death
• persist for several days after poisoning
• 10 of cases have irreversible effects
• respiratory failure
• nephrogenic diabetes

8
Toxicity

• Chronic
• teratogenicity
• lithium freely crosses placental barrier
• full equilibrium in maternal and umbilical cord
  blood
• newborn plasma lithium levels identical to mother
• diminishes quickly after birth

9
Toxicity

• Chronic
• transported via breast milk
• milk/infant blood concentration 1/3 to 1/2 of
  maternal blood concentration
• lower dose still harmful
• lessened ability for detoxification
• effects
• cardiovascular defects
• dextrocardia and aortic coarctation
• Epsteins anomaly most common

10
Toxicity

• Chronic
• theories for teratogenic effects
• longer half-life in infants
• 68 hours for infants
• 20 hours in adults
• hormonal interaction
• reduction in circulating thyroid hormone
• altered growth hormone levels

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Mechanism of Toxicity

• Ingestion and absorption
• rapidly absorbed from G.I. tract
• appears in tissue fluid and organs within minutes
• eight hours for complete absorption
• peak concentration observed after 2-4 hours
• distributed throughout body
• initially in extracellular fluid
• accumulates slowly in various tissues

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Mechanism of Toxicity

• Attack of target site
• target central nervous system
• carried via circulatory system to brain
• can cross blood-brain barrier
• cerebrospinal fluid concentration 40-50 of
  plasma concentration
• no binding to plasma proteins
• chemically intact at target site
• important for transport across membranes

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Mechanism of Toxicity

• Transport across membranes
• several hypotheses
• similar to transport of sodium and potassium
• monovalent cations
• may substitute for sodium and potassium in
  transport processes
• voltage-gated ion channels
• allow sodium ions into cell
• lithium ions replace sodium and cross membrane

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Mechanism of Toxicity

• Transport across membranes
• direct active transport
• utilizes ATPase
• generates action potential and transmits nerve
  impulse
• lithium displaces sodium in this process
• can only support single action potential
• affects nerve excitation, synaptic transmission,
  and neuronal metabolism

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Mechanism of Toxicity

• Manifestation of mechanism
• lithium affects neurotransmitters in brain
• inhibitory effect
• norepinephrine
• dopamine
• stimulatory effect
• serotonin
• superstimulation/superinhibition responsible for
  toxic effects
• seizures, delirium, coma and death

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Mechanism of Toxicity

• Excretion
• rapid
• half-life of 20 hours in adult humans
• primarily via kidneys
• 80 of lithium reabsorbed in kidneys
• 97 of dose excreted within 10 days
• secondary excretion routes
• feces
• sweat

17
Treatments

• Diuretics
• lowers plasma concentration of lithium
• counteracted with fluid administration to avoid
  dehydration
• Acetazolamide
• facilitates excretion via kidneys
• used alone and with other drugs
• Dialysis
• extremely severe poisonings

18
Current Status

• Remains commonly used for therapeutic purposes
• Additional study required to isolate specific
  mechanism of toxicity
• Chronic effects remain widely debated
• Patients using lithium carefully monitored for
  any evidence of toxicity

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References

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