030515 toxic and metabolic dis

Question 1

how to recognize a metabolic disorder

Answer 1

suspect metabolic disorder whenever clinical presentation doesn’t fit a medical textbook, doesn’t respond to common tx

Question 2

suspicious presentations for metabolic disorder

Answer 2

unexplained lethargy, confusion, somnolence
unexplained metabolic acidosis/alkalosis
excessive lactate or ketosis
persistent or recurrent hypoglycemia
unusual MRI, EEG, pathology

Question 3

GM2 gangliosidoses

Answer 3

caused by deficiency of lysosomal enzymes, resulting in accumulation of gangliosides

types: hexoaminidase A deficiency (Tay Sachs), heosaminidase B (sandhoff dis), etc

Question 4

clinical signs of Tay Sachs

Answer 4

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

Question 5

pathology for Tay Sachs

Answer 5

enlarged ballooned neurons filled w PAS positive material (stored ganliosides)

EM: MEMBRANOUS CYTOPLASMIC BODIES (LOOK LIKE SWIRLS)

Question 6

Krabbe’s disease

Answer 6

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

Question 7

clinical signs of Krabbe’s dis

Answer 7

normal development
onset at 3-6 months: irritability, development ceases. deterioration of motor fxn. optic atrophy, blindness

death by 2 years

Question 8

pathology of Krabbe’s dis

Answer 8

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

Question 9

metachromatic leukodystrophy

Answer 9

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

Question 10

signs of metachromatic leukodystrophy

Answer 10

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

Question 11

pathology of metachromic leukodystrophy

Answer 11

marked loss of myelin

metachromasia of white matter deposits

Question 12

adrenoleukodystrophy

Answer 12

peroxisomal disorder
decreased activity of very long chain fatty acyl-coA synthetase in peroxisomes

X linked

Question 13

clinical signs of adrenoleukodystroph

Answer 13

onset 5-9 yrs or 11-21 yrs
dementia, visual and hearing loss, seizures
adrenal insufficiency follows

adrenomyeloneuropathy-occurs in adults. motor signs

Question 14

pathology of adrenoleukodystrophy

Answer 14

severe demyelination in white matter

PERIVASCULAR INFLAMMATION

Question 15

pathology of hepatic encephalopathy

Answer 15

Alzheimer type II astrocytes (no visible cytoplasm, cleared out nucleus)

Question 16

pathology of hypoglycemia

Answer 16

mimics ischemic findings

red neurons

Question 17

symptoms of Wernicke encephalopathy

Answer 17

ophthalmoplegia, nystagmus
ataxia
confusion, disorientation, eventual coma

Question 18

pathology of Wernicke encephalopathy

Answer 18

pallor, prominent vessels, myelin loss

lesions are in mamillary bodies, dorsomedial thalamus, around 3rd and 4th ventricles

Question 19

symptoms of Korsakoff psychosis

Answer 19

loss of anterograde episodic memory, confabulation, preserved inteliggence

thought to result from repeated episodes of Wernicke’s. no pathology diff from Wernicke’s

Question 20

symptoms of vit B12 deficiency

Answer 20

ataxia, Romberg, spasticity, decreased reflexes, mental status changes

Question 21

pathology of vit B12 deficiency

Answer 21

CNS and PSN involved

sp cord: anterior and lateral corticosp tracts and posterior columns are vacuolated and demyelinated

Question 22

carbon monoxide damage on CNS

Answer 22

binds to areas rich in iron (GLOBUS PALLIDUS, substantia nigra) and causes NECROSIS

Question 23

chronic alcohol toxicity-damage to CNS?

Answer 23

CEREBELLAR DEGENERATION

Question 24

damage of radiation toxicity to brain

Answer 24

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

Question 25

methotrexate’s damage to brain

Answer 25

intrathecal or intraventricular administration in combo w radiation may produce disseminated necrotizing leukoencephalopathy, coagulative necrosis w mineralization