Toxic Injury Flashcards
A 42-year-old man has had 6 to 15 drinks per day for the last 15
years. He is healthy overall, but has difficulty with tandem gait. Which is
the most common site of central nervous system (CNS) atrophy associated
with chronic alcoholism?
a. The superior vermis
b. Wernicke’s area
c. The supraorbital gyrus
d. The angular gyrus
e. The flocculus
The answer is a.( Victor, pp 1224–1226.)The superior vermis of the
cerebellum loses Purkinje cells and exhibits atrophy of the molecular layer
in alcoholic persons after years or decades of ethanol use. Alcoholic
patients may have gait instability and limb ataxia associated with this
injury, but the clinical signs are usually fairly mild considering the histo-logic damage done by ethanol. White matter in the cerebellum is relatively
unaffected
Triorthocresyl phosphate (TOCP) is an organophosphate that may
cause lethal neurologic complications by
a. Eliciting massive intracerebral edema
b. Causing a severe motor polyneuropathy
c. Producing widespread CNS demyelination
d. Allowing CNS infections secondary to generalized immunosuppression
e. Inducing status epilepticus
The answer is b. ( Victor, pp 1281–1282.) Triorthocresyl phosphate
damages both upper and lower motor neurons. This damage is usually
severe and likely to be permanent. Death may occur within a few days of
severe exposure. This material is a common constituent of rat poisons,
roach powders, and other insecticides. Oral ingestion is usually required
for substantial toxicity. The acute symptoms of poisoning reflect the anti-cholinesterase activity of the poison. This produces headaches, vomiting,
abdominal cramps, excessive sweating, wheezing, and twitching.
A 1-year-old child is brought to the emergency room with an acute
encephalopathy. It is determined that the etiology is lead intoxication. With
severe lead poisoning, very young children may die of brain herniation sec-ondary to
a. Subdural hematomas
b. Epidural hematomas
c. Intracerebral hemorrhage
d. Obstructive hydrocephalus
e. Massive brain edema
The answer is e.( Victor, pp 1277–1278.) Lead poisoning may cause
ataxia and tremor in children exposed to relatively low levels. Chronic
exposure routinely impairs psychomotor development and may lead to
substantial retardation in very young children. Brain edema develops with
toxic lead exposure in infancy and may be lethal even with efforts to relieve
the intracranial pressure. Children are exposed to lead in many forms in
the environment, including lead-based paint chips from old construction
and lead-tainted soil in areas with heavy vehicular traffic.
A 30-year-old man takes a can of beer out of his refrigerator at the
end of the day and rapidly swallows a mouthful of its contents before he
realizes it is not beer. Within a few minutes he develops severe abdominal
cramps, blurred vision, twitching, and loss of consciousness. His wife noti-fies emergency medical personnel that she had placed some roach spray in
the beer can for storage and had left it in the refrigerator to deal with
roaches that were nesting there. She claims that she forgot to advise her
husband of this. Emergency personnel check the insecticide brand and
determine that it is an organophosphate. To counteract the cholinesterase-inhibiting activity of the organophosphate poison, the man should receive
a. Methacholine
b. Pyridostigmine
c. Physostigmine
d. Edrophonium
e. Atropine
The answer is e.( Victor, pp 1281–1282.) Methacholine is a choliner-gic agent and would be expected to worsen the symptoms exhibited by this
man. Pyridostigmine, physostigmine, and edrophonium are all cholineste-rase inhibitors used in the evaluation or treatment of myasthenia gravis, and
they too would only hasten this man’s deterioration. Atropine is usually given
in combination with pralidoxime. This man is at most immediate risk of
severe bronchospasm and diaphragmatic paralysis with subsequent respiratory arrest. Even if the patient does survive the acute poisoning, he is at risk
for a delayed deterioration of the motor system, which may itself prove fatal
and which does not respond to atropine treatment.
A man working in a poorly regulated felt processing plant develops
tremors and memory disturbances over the course of months. He seeks
medical help when tremors of his tongue and lips became embarrassing
and he is injured during a fall. His family notes progressive irritability and
depression. On neurologic examination, he has prominent gait ataxia, limb
and facial tremors, and decreased pain and temperature sense in his feet.
(SELECT 1 TOXIN)
Choose the toxin that is likely to produce each clinical picture.
a. Lead
b. Arsenic
c. Manganese
d. Mercury
e. Carbon monoxide
f. Ergot
g. Nitrous oxide
The answer is d.( Victor, pp 1280–1281.) The “Mad Hatter” of Alice
in Wonderland was a familiar site in the nineteenth century. Persons who
cured felt (used in the manufacture of hats) with nitrate of mercury often
developed pronounced personality changes, tremor, and ataxia. This type
of poisoning is now more typically seen in paper, pulp, and electrochem-ical plants that use phenyl mercury as part of the manufacturing process.
Pathologic changes in the CNS are usually prominent in the cerebellum
and include extensive damage to the granular cell layer of the cerebellum.
The calcarine cortex of the occipital lobe is also especially vulnerable,
and damage to this tissue correlates with constriction of the visual fields.
While vacationing in Latin America, a student buys a brightly
painted glazed ceramic pitcher. He drinks orange juice from the pitcher
every night while studying. Within 4 months of starting this practice, he
develops weakness in both wrists. He consults a physician, who finds
weakness on dorsiflexion of both hands, unassociated with any sensory
deficits. An EMG reveals evidence of a peripheral motor neuropathy.
(SELECT 1 TOXIN)
Choose the toxin that is likely to produce each clinical picture.
a. Lead
b. Arsenic
c. Manganese
d. Mercury
e. Carbon monoxide
f. Ergot
g. Nitrous oxide
The answer is a.( Victor, pp 1278–1279.) Decorative paint and glazes
manufactured and sold outside the United States may have very high lead
levels. Even mildly acidic solutions, such as orange juice, may leach
enough lead out of the paint to produce symptoms in persons exposed over
a protracted period to fluids contaminated with the lead. Bilateral neu-ropathies may develop in adults exposed to lead, and the radial nerves are
the most common sites of damage. This neuropathy at its most severe will
produce wrist and finger drops as well as occasionally very mild sensory
abnormalities in the distribution of the radial nerves. Signs associated with
the lead neuropathy may include abdominal pain, constipation, anemia,
basophilic stippling of erythrocyte precursors, and a linear discoloration
along the gingival margin (lead lines). Penicillamine is used as a chelating
agent to reduce the body load of lead.
A 45-year-old woman reports to the police her discovery that her
husband has added a suspicious material to her food. She has experienced
matrimonial problems for several years and has developed progressive
fatigue with frequent headache over the prior 3 months. She consulted a
physician when she developed recurrent bouts of severe stomach pain and
was told by neighbors that she had been talking to herself and attacking
invisible assailants. The physician noted that she had an unexplained ane-mia and white lines running transversely across her fingernails. She also
has had problems with her memory, excessive drowsiness, and a sensori-motor neuropathy with absent tendon reflexes. The physician sent a sam-ple of her hair for analysis and found a neurotoxin present. (SELECT 1
TOXIN)
Choose the toxin that is likely to produce each clinical picture.
a. Lead
b. Arsenic
c. Manganese
d. Mercury
e. Carbon monoxide
f. Ergot
g. Nitrous oxide
The answer is b.( Victor, p 1279.) Acute poisoning with arsenic may
cause tonic-clonic seizures or a less dramatic encephalopathy. Hemolysis
may be substantial and mucosal irritation may be evident. Death may
develop with circulatory collapse if the dose of arsenic is substantial
enough. The polyneuropathy that develops with chronic poisoning is resis-tant to treatment with chelating agents such as BAL. If the patient survives
the poisoning, peripheral nerve damage resolves over the course of months
or years.
An Eastern European immigrant who recently arrived in the United
States is brought to the emergency room after a seizure. He first developed
seizures at the age of 30 and never received treatment. Neurologic exami-nation reveals fasciculations and occasional myoclonus. He is ataxic and
has absent deep tendon reflexes. A sensory neuropathy is evident in his
legs. Ulcers are evident on his fingers and toes. He acknowledges that his
diet was very limited before he immigrated to the United States, and states
that most of his calories were derived from rye grains. (SELECT 1 TOXIN)
Choose the toxin that is likely to produce each clinical picture.
a. Lead
b. Arsenic
c. Manganese
d. Mercury
e. Carbon monoxide
f. Ergot
g. Nitrous oxide
The answer is f. ( Victor, p 1275.) This man’s history suggests a nutri-tional disorder rather than poisoning, but his clinical picture is consistent
with chronic ergotism. Ergot is a potent vasoconstricting agent derived
from the rye fungus, Claviceps purpurea. Currently, the contamination of
bread with this material is unlikely in developed nations, but it is still a
problem in areas with antiquated agricultural techniques. Chronic ergot
poisoning is associated with histologic changes in the CNS, which include
degeneration of the posterior columns and dorsal roots. A peripheral neu-ropathy is also evident, but persons at risk for this disorder are also at risk
for other nutritional disturbances that may produce neuropathy.
A 38-year-old miner develops a shuffling gait, tremor, and drooling.
His speech is difficult to understand and trails off in volume until it is
inaudible. He consults a physician because of easy fatigability and frequent
falls. Cogwheel rigidity is evident in his arms and legs. His tremor is most
evident when his limbs are at rest. (SELECT 1 TOXIN)
Choose the toxin that is likely to produce each clinical picture.
a. Lead
b. Arsenic
c. Manganese
d. Mercury
e. Carbon monoxide
f. Ergot
g. Nitrous oxide
The answer is c. ( Victor, pp 1279–1280.) Manganese inhalation by
miners produces a clinical picture similar to that seen with hepatolenticu-lar degeneration (Wilson’s disease). Parkinsonism is the most prominent
feature, but axial rigidity and dystonia may also develop. Neuronal loss is
evident in several areas of the brain, including the globus pallidus, puta-men, caudate, hypothalamus, and cerebellum. Treatment with L-dopa is
usually less effective with this heavy metal injury than it is with Parkinson’s
disease. Agents more likely to produce parkinsonism in the general popu-lation include phenothiazines, butyrophenones, and metoclopramide.
Metoclopramide (Reglan) is used increasingly after gastrointestinal surgery
to manage nausea and other signs of gastrointestinal irritability. Although
most physicians do ask about exposure to reserpine-like medications or
phenothiazines, other drugs that may cause parkinsonism in susceptible
persons are sometimes overlooked
A 35-year-old woman is rescued from a burning building. She is
comatose on arrival in the ER. Her skin is cyanotic. Computed tomography
(CT) scan of her head shows mild cerebral edema. After intensive care in a
burn unit, she recovers markedly, but 2 weeks later, she begins to develop
dystonic posturing and bradykinesia. A CT scan now shows hypodensities
in the globus pallidum bilaterally. (SELECT 1 TOXIN)
Choose the toxin that is likely to produce each clinical picture.
a. Lead
b. Arsenic
c. Manganese
d. Mercury
e. Carbon monoxide
f. Ergot
g. Nitrous oxide
The answer is e.( Victor, p 1180.) Carbon monoxide (CO) poisoning
can be seen in victims of fires, in those who attempt suicide by carbon
monoxide inhalation, or in those who are otherwise exposed to the gas in
an unventilated setting. Because of its greater affinity for hemoglobin than
oxygen, CO reduces oxygen in the blood and leads to prolonged hypoxia
and acidosis. Symptoms may range from confusion and headache at car-boxyhemoglobin levels of 20% to coma, posturing, and seizures at levels of
50 to 60%. Characteristic of CO poisoning is delayed neurologic deteriora-tion occurring 1 to 3 weeks after the initial event. Typically, this takes the
form of an extrapyramidal disorder with Parkinsonian gait and bradykine-sia. Imaging may show the classic hypodensities in the globus pallidum
bilaterally
A 45-year-old Portuguese immigrant develops abdominal pain in the
early evening after eating grouper for lunch. He later develops fatigue,
headache, and paresthesias. He reports on examination that a cold tuning
fork feels excessively hot to the touch. (SELECT 1 SUBSTANCE)
Choose the toxic substance likely to produce each clinical picture.
a. Ciguatoxin
b. Botulinum toxin
c. Saxitoxin
d. Tick paralysis
e. Ionizing radiation
f. Phencyclidine hydrochloride (PCP)
g. Cocaine
h. Lathyrus sativus
i. Ammonia
The answer is a.( Bradley, pp 1535–1536.) Ciguatera food poisoning
occurs in the tropics, but may affect parts of the southern coastal United
States, including Florida and Hawaii. Many different toxins are produced
by dinoflagellates, which are in turn consumed by reef fish. Ciguatoxin is
the best known, and it acts on voltage-gated sodium channels, leading to
increased permeability to sodium and increased excitability. Symptoms
include abdominal discomfort, nausea, vomiting, and diarrhea, followed
by neurological symptoms such as paresthesias, headache, fatigue, ataxia,
and myalgias. About 80% of patients complain of a peculiar sensory phe-nomenon of temperature reversal, specifically characterized by a tendency
for cold objects to feel uncomfortably hot. Occasionally, cardiovascular
symptoms, including hypotension or shock, may occur due to the effects of
the toxin on cardiac muscle cells. Intravenous mannitol appears to have
some treatment benefit
A 30-year-old refugee from sub-Saharan Africa is malnourished. She
has a subacute spastic paraparesis and gait instability. Cognition, sensory,
and cerebellar functions are intact. (SELECT 1 SUBSTANCE)
Choose the toxic substance likely to produce each clinical picture.
a. Ciguatoxin
b. Botulinum toxin
c. Saxitoxin
d. Tick paralysis
e. Ionizing radiation
f. Phencyclidine hydrochloride (PCP)
g. Cocaine
h. Lathyrus sativus
i. Ammonia
The answer is h. ( Bradley, p 1532.)Lathyrism is a condition char-acterized by slow or subacute onset of spastic paraparesis in the setting of
excessive dietary reliance on the chickling pea ( L. sativus ) or other mem-bers of the Lathyrus species. The syndrome typically occurs in epidemics
in the setting of famine or war, in which people are forced to rely exces-sively on this legume. The toxin is thought to be β -N- oxalylamino-L -alanine (BOAA), an excitatory neurotransmitter that can induce the dis-ease in primate models. Damage in the CNS is primarily in spinal cord
tracts, especially the corticospinal and spinocerebellar tracts. Demyelina-tion is evident in some affected persons in the lateral and posterior
columns of the spinal cord
A 5-year-old girl with long hair is hospitalized during August with a
rapidly ascending flaccid quadriparesis over 2 days. She had been camping
in the woods with her family during the preceding week. She develops
neck, eye, and bulbar paralysis over the 8 h after admission, ultimately
requiring mechanical ventilation. Spinal fluid protein and cell levels are
entirely normal. (SELECT 1 SUBSTANCE)
Choose the toxic substance likely to produce each clinical picture.
a. Ciguatoxin
b. Botulinum toxin
c. Saxitoxin
d. Tick paralysis
e. Ionizing radiation
f. Phencyclidine hydrochloride (PCP)
g. Cocaine
h. Lathyrus sativus
i. Ammonia
The answer is d.( Bradley, p 1531.) This girl has a clinical syndrome
not unlike Guillain-Barré syndrome (GBS). The rapidity of progression,
however, and the absence of an elevated spinal fluid protein level, make
GBS less likely and tick paralysis more likely. Tick paralysis commonly
affects young children and particularly those with long hair that may
obscure the tick’s location. A careful search for the organism—either Ixodes
holocyclus (Australia) or a Dermacentor tick (North America)—is required
in cases of rapidly ascending paralysis of unclear etiology. Removal of the
tick will produce dramatic improvement within hours. The responsible
toxin of the Australian tick, called holocyclotoxin, interferes with the
presynaptic release of toxin at the neuromuscular junction
A 34-year-old schizophrenic man with a history of Hodgkin’s disease
in remission since treatment 10 years ago presents with a right middle cere-bral artery territory stroke. He is found to have bilateral carotid bruits.
There is no history of hypertension, diabetes, or hypercholesterolemia. He
does smoke cigarettes. (SELECT 1 SUBSTANCE)
Choose the toxic substance likely to produce each clinical picture.
a. Ciguatoxin
b. Botulinum toxin
c. Saxitoxin
d. Tick paralysis
e. Ionizing radiation
f. Phencyclidine hydrochloride (PCP)
g. Cocaine
h. Lathyrus sativus
i. Ammonia
The answer is e.( Victor, pp 728–729.) Ionizing radiation may cause
accelerated atherosclerosis. Patients with Hodgkin’s disease undergoing
mantle irradiation may present years later with carotid stenosis due to ath-erosclerosis. Surgical treatment is made more difficult by the radiation,
which can cause scarring of the tissues surrounding the vessels, rendering
dissection of the vessel more difficult
A 27-year-old man with idiopathic cardiomyopathy and right heart
failure is admitted to the intensive care unit. Over several days his mental
status worsens. He is disoriented and inattentive, but able to follow com-mands. He has prominent asterixis bilaterally. He improves 24 h later after
lactulose is administered. (SELECT 1 SUBSTANCE)
Choose the toxic substance likely to produce each clinical picture.
a. Ciguatoxin
b. Botulinum toxin
c. Saxitoxin
d. Tick paralysis
e. Ionizing radiation
f. Phencyclidine hydrochloride (PCP)
g. Cocaine
h. Lathyrus sativus
i. Ammonia
The answer is i. ( Bradley, pp 1476–1480.) In its early stages, hepatic
encephalopathy is characterized by a decrease in the level of alertness; irri-tability or depression; tremor; and asterixis. As it progresses, lethargy, para-noia, bizarre behavior, dysarthria, nystagmus, and pupillary dilatation may
occur. There is good evidence that ammonia is an important factor in the
development of encephalopathy, though other mechanisms, including dis-ordered amino acids and neurotransmitters—particularly γ-aminobutyric
acid (GABA) and benzodiazepine metabolites—and short-chain fatty acids
may play a role as well. Lactulose is the most effective agent in the treat-ment of hepatic encephalopathy. It appears to work by allowing bacteria
in the gastrointestinal tract to assimilate ammonia. Hepatologists have
recently updated previous recommendations regarding dietary restrictions
on protein in patients with hepatic encephalopathy because it has been rec-ognized that protein consumption is necessary to allow for recovery of liver
function.
