030515 toxic and metabolic dis Flashcards
how to recognize a metabolic disorder
suspect metabolic disorder whenever clinical presentation doesn’t fit a medical textbook, doesn’t respond to common tx
suspicious presentations for metabolic disorder
unexplained lethargy, confusion, somnolence unexplained metabolic acidosis/alkalosis excessive lactate or ketosis persistent or recurrent hypoglycemia unusual MRI, EEG, pathology
GM2 gangliosidoses
caused by deficiency of lysosomal enzymes, resulting in accumulation of gangliosides
types: hexoaminidase A deficiency (Tay Sachs), heosaminidase B (sandhoff dis), etc
clinical signs of Tay Sachs
normal at birth
6 mos-psychomotor retardation
progresses-blindness, motor incorrdination, flaccidity, mental deterioration, decerebrate state
cherry red spot in macula
death by 2-3 years
pathology for Tay Sachs
enlarged ballooned neurons filled w PAS positive material (stored ganliosides)
EM: MEMBRANOUS CYTOPLASMIC BODIES (LOOK LIKE SWIRLS)
Krabbe’s disease
also called globoid cell leukodystrophy
lysosomal storage dis
autosomal recessive
deficiency of GALACTOCEREBROSIDE-B-GALACTOSIDASE (results in accumulation of toxic compound that injures oligodendrocytes. galactocerebroside is component of myelin sheaths)
both CNS and PNS affected
clinical signs of Krabbe’s dis
normal development
onset at 3-6 months: irritability, development ceases. deterioration of motor fxn. optic atrophy, blindness
death by 2 years
pathology of Krabbe’s dis
globoid macrophages (multiple nuclei per cell)
loss of myelin
decreased numbers of oligodendrocytes
EM: globoid macrophages contain crystalloid straight or tubular profiles (needle like inclusions)
etc
metachromatic leukodystrophy
lysosomal storage dis autosomal recessive deficiency of ARYL SULFATASE A metachromatic lipids (sulfatides) accumulate in brain, peripheral nerves, and kidney
sulfatide accumulation causes breakdown of myelin
signs of metachromatic leukodystrophy
late infantile, intermediate or juvenile
each type presents w gait disorder and motor symptoms
death in 5-10 yrs
adult-usually present w psychosis and cognitive impairment
pathology of metachromic leukodystrophy
marked loss of myelin
metachromasia of white matter deposits
adrenoleukodystrophy
peroxisomal disorder
decreased activity of very long chain fatty acyl-coA synthetase in peroxisomes
X linked
clinical signs of adrenoleukodystroph
onset 5-9 yrs or 11-21 yrs
dementia, visual and hearing loss, seizures
adrenal insufficiency follows
adrenomyeloneuropathy-occurs in adults. motor signs
pathology of adrenoleukodystrophy
severe demyelination in white matter
PERIVASCULAR INFLAMMATION
pathology of hepatic encephalopathy
Alzheimer type II astrocytes (no visible cytoplasm, cleared out nucleus)
pathology of hypoglycemia
mimics ischemic findings
red neurons
symptoms of Wernicke encephalopathy
ophthalmoplegia, nystagmus
ataxia
confusion, disorientation, eventual coma
pathology of Wernicke encephalopathy
pallor, prominent vessels, myelin loss
lesions are in mamillary bodies, dorsomedial thalamus, around 3rd and 4th ventricles
symptoms of Korsakoff psychosis
loss of anterograde episodic memory, confabulation, preserved inteliggence
thought to result from repeated episodes of Wernicke’s. no pathology diff from Wernicke’s
symptoms of vit B12 deficiency
ataxia, Romberg, spasticity, decreased reflexes, mental status changes
pathology of vit B12 deficiency
CNS and PSN involved
sp cord: anterior and lateral corticosp tracts and posterior columns are vacuolated and demyelinated
carbon monoxide damage on CNS
binds to areas rich in iron (GLOBUS PALLIDUS, substantia nigra) and causes NECROSIS
chronic alcohol toxicity-damage to CNS?
CEREBELLAR DEGENERATION
damage of radiation toxicity to brain
delayed effects (months to years)
clinical symptoms of a mass lesion
large area of coagulative necrosis, primarily in white matter. vessels w thickened walls
induction of neoplasms
