Toxic & Acquired Metabolic Diseases Flashcards
What are the characteristics of B12 (cobalamin) deficiency?
- normochromic, macrocytic anemia
- causes subacute degeneration of the spinal cord
- -ascending posterior columns
- -descending pyramidal tracts
–Histo: swelling of myelin layers which produces vacuoles, beginning at mid-thoracic level of spinal cord
What are the symptoms and treatment of B12 (cobalamin) deficiency?
Initially: B/L symmetrical numbness, tingling, and slight ataxia in the lower extremities
Progression: spastic weakness in lower extremities; late course may result in complete paraplegia
–B12 replacement can improve the disease course unless complete paraplegia has occurred
What are the symptoms of a B1 (thiamine) deficiency (aka Wernicke Encephalopathy)?
- psychotic symptoms
- ophthalmoplegia
Progression to: Korsakoff Syndrome (irreversible)
- -short-term memory disturbances
- -confabulation
Beriberi = cardiac failure
What are the potential causes of B1 (thiamine) deficiency and the treatment?
- chronic alcoholism
- gastric carcinomas
- chronic gastritis
- persistent vomiting
Tx: thiamine replacement (Banana Bags)
What is the histology of B1 (thiamine) deficiency?
-hemorrhage and necrosis of mammillary bodies and the walls of the 3rd and 4th ventricles
What areas of the brain are most affected by hypoglycemia?
- large pyramidal neurons of the cerebral cortex
- pyramidal neurons of Sommer Sector (CA1) of hippocampus
- Purkinje cells of cerebellum
What can be seen on gross morphology of the brain d/t hypoglycemia?
-PSEUDOLAMINAR NECROSIS of the deep layers of the cortex
What are the neuro aspects of hyperglycemia?
- ketoacidosis
- hyperosmolar coma
- dehydration
- confusion/stupor
- NO significant morphological brain changes
–must correct fluids gradually to avoid severe cerebral edema
What are the neuro aspects of Hepatic Encephalopathy?
- glial response in the CNS
- elevated ammonia and proinflammatory cytokines
- Alzheimer Type II cells in cortex, basal ganglia
- -astrocytes w/ large nuclei and minimal cytoplasm
- -also seen in Wilson Disease
What are the neuro aspects of carbon monoxide?
–hypoxia d/t altered oxygen-carrying capacity of RBC’s
–selective injury to layers III and V of cerebral cortex, Sommer Sector of the hippocampus, and Purkinje cells
–B/L necrosis of globus pallidi (more common in CO hypoxia than in other causes of hypoxia)
–later, demyelination of white matter tracts
What are the neuro aspects of methanol?
- degeneration of retinal ganglion cells
- blindness
- B/L putamen necrosis w/ severe exposure
-formate is the major toxic metabolite; disrupts oxphos
What are possible neuro symptoms of chronic ethanol abuse?
- 1% develop cerebellar dysfxn
- -truncal ataxia
- -unsteady gait
- -nystagmus
What is the neuro histology of chronic ethanol abuse?
- atrophy and loss of granule cells in anterior vermis
- Advanced Cases: “Bergmann Gliosis” b/w the depleted granule cell layer and the molecular cell layer (loss of Purkinje cells, proliferation of adjacent astrocytes)
What are the neuro effects of radiation?
-exposure to high dose: intractable nausea, confusion, convulsions, rapid onset of coma, and death
- delayed effects can occur months to years later
- -HA, N/V, papilledema
What types of tumors can radiation induce years after the exposure?
- sarcomas
- gliomas
- meningiomas
What is seen on histology after radiation exposure?
- COAGULATIVE NECROSIS (primarily white matter) involving all tissue elements in the area, w/ adjacent edema
- vascular fibrinoid necrosis (thick walls w/ intramural fibrin-like material)
What is Neuronal Ceroid Lipofuscinoses (NCL)?
- autosomal recessive lysosomal storage disease
- accumulation of lipofuscin leading to neuronal dysfxn
- blindness, mental/motor deterioration, seizures, death
What is Krabbe Disease?
- autosomal recessive leukodystrophy
- deficiency in GALACTOSYLCERAMIDASE
-accumulation of galactocerebroside, so it gets shunted to an alternate pathway which creates galactosylsphingosine (cytotoxic to oligodendroglia)
What are the symptoms and potential treatment of Krabbe Disease?
- onset at 3 to 6 months; death by age 2
- stiffness and weakness
- feeding difficulties
Tx: potential treatment w/ cord blood prior to becoming symptomatic
What is seen on histology of Krabbe Disease?
- loss of myelin and oligodendrocytes in CNS and PNS
- neurons and axons are spared
- aggregation of engorged macrophages (globoid cell)
What is Metachromatic Leukodystrophy?
- multiple mutations on 22q
- autosomal recessive disease resulting from arylsulfatase deficiency and accumulation of cerebroside sulfate
- the sulfatides that accumulate inhibit the differentiation of oligodendrocytes
Describe the two forms of Metachromatic Leukodystrophy.
Late Infantile/Juvenile:
- most common
- motor symptoms
- gradual progression
- death in 5 to 10 yrs
Adult:
- psychiatric and cognitive symptoms initially
- motor deficits later
What is the potential treatment for Metachromatic Leukodystrophy?
- bone marrow stem cell transplant
- -as long as it’s before the neurological deficits
What is seen on histology in Metachromatic Leukodystrophy?
- demyelination
- gliosis (astrocyte hypertrophy and hyperplasia)
-macrophages w/ cytoplasmic vacuoles containing crystalloid structures composed of sulfatides that bind w/ toluidine blue to create the metachromasia
