Toxic/metab/nutirtional diseases Flashcards
acute alcohol intoxication in large quantity cause death by
finding in brain
central cardiorespiratory paralysis
massive cerebral edema, flattening of gyri, obliteration of sulci
chronically effect of alcohol on cerebral hemispheres
hemispheres shrink via diffuse loss of white matter (atrophy) and meningeal fibrosis
some neurons lost from frontal cortex with cell body shrink, retract dendrites, incr lipofuscin
chronically effect of alcohol on cerebellum
degeneration of superior vermis
folial crests are more affected than deeper structures (and lose purkinje, granule) with incr astrocytes
clinical presentation of alcoholic cerebellar degeneration
1) truncal instab
2) leg ataxia
3) wide based gait
how does cirrhotic liver affect brain
liver can’t process toxins –> heepatic encephalopathy likely due to ammonia
change proportion of excit/inhib NT or make false NT
hepatic cirrhosis characterized by what symptoms
1) confusion, forgetfulness
2) asterixis
3) stupor, coma
define hepatic encpehalopahty and mechanism of ammonia intox
fulminant liver failure due to high ICP from high blood ammonia from GI hemorrhage and severe cirrhosis (above 200)
ammonia from protein catabolism and urease-containing bacteria
ammonia not convert to urea (portal HTN) –> ammonia enter BBB and taken up by astrocytes
astrocyte’s glutamine synthetase for detox overwhelmed
histology of astrocytes in hepatic encephalopathy
alzheimer type 2 cells
astrocytes with
1) swollen nuclei
2) little cytoplasm
in deep cortex, globus pallidus, dentate nucelus of cerebellum
wernicke’s encephalopathy and korsakoff psychosis due to
assoc with
histo changes
thiamine b1 deficiency
assoc with
1) chronic etoh
2) poor food intake
3) absorb problem (G tube and hyperemesis )
4) malutilization and incr excretion
edema, necrosis, demyelination, neuron loss, gliosis
wernicke’s encephalopathy and korsakoff psychosis precipitated by
sudden glucose intake without thiamine
B1 needed for transketolase fxn and cofactor for glucose metab
triad of wernicke’s encephalopathy
1) ataxia
2) nystagmus
3) confusion
reversible if treat with thiamine
korsakoff syndrome
1) memory loss
2) confabulation = create false memories to fill gaps
irreversible
what structure involved in wernicke’s and korsakoff
mamillary bodies but also
1) wall of 3rd ventricle
2) periaquductal
3) inferior colliculi and thalamus
4) floor of 4th ventricle
acute stage of wernicke’s and korsakoff histologically
macro and microscopic petechial hemorrhage
prominant and dilated capillaries
imaging of wernicke’s and korsakoff
disrupt BBB from cytotoxic edema causing astrocyte swelling –> gives off NO –> change glutamate –> more free radicals
subacute vs acute wernicke’s and korsakoff
subacute
1) myelin lost
2) microglia and macrophage influx
3) fibrous gliosis
chronic
1) loss neurons
2) hemosiderin
3) mamillary atrophy
treatment of wernicke’s and korsakoff
IV thiamine
describe central pontine myelinolysis
symm demyelination affects pons usu from rapid correction of hyponatremia
symptoms of central pontine myelinolysis
triangular regions of demyelination with spared axons and neurons
quadriparesis
pseudobulbar palsy
pseudocoma
sites of vulnerability in central pontine myelinolysis
ventral pons
extrapontine sites
treatment of central pontine myelinolysis
slow treatment of hyponatremia
colbalamin deficiency
occurs due to
importance of colbalimin
decr intake (strict vegan or GI cancer), pernicious anemia (most common) and immune mediated atrophic gastritis
cobalimin impt for methionine synthase for myelination
colbalamin deficiency can cause
megaloblastic anemia
colbalamin deficiency
early signs
later sign
paresthesias and ataxia (loss of DC/ML from swelling of myelin) and lower limb paresthesia
spastic paraparesia
ataxia
lower limb/trunk sensory defect
treatable dementia from patchy white matter dmg, psychoses
incontinence
orthostatic hypotension
colbalamin deficiency
affects where
mechanism of myelin loss
ascending (sensory) and descending tracts (motor in the cord white matter esp lower cervical and thoracic (subacute combined degeneration)
1) initial = spongy vacuolization of white matter
2) myelin break down
3) macrophage influx and axon degenerate
colbalamin deficiency
treat with
IV B12 supplementation
Wilson’s disease
genetics
presents age
AR (chorm 13) disorder of copper metabolism
present in children or young adult
Wilson’s disease
differnece btwn child and adult
child = copper accum in liver –> jaundice
adult = copper accum in CNS esp lentiform nucleus –> basal ganglia degeneration (
Wilson’s disease
degeneration of basal ganglia causes
movement disorders
- flap tremor, spasticity
- dysarthria
- limb incoordination
- gait problems, involuntary movement
- dystonia
Wilson’s disease
most commonly affects where in brain
cells on histo
putamen
globus pallidus
Wilson’s disease
cells on histo
alzheimer type 2 just like hepatic encephalopathy (swollen nuclei, small cyto)
damaged neurons via free radicals by copper or oxid of membrane lipids
astrocytosis
treatment of wilson’s disease
chelating agents (pencillamine or trientine)
fatal if not treat
what part of brain is affected by methanol toxicity
hemorrhagic necrosis in putamen
fetal alcohol syndrome
features
poor motor skills
learning difficulties
mental retardation
indistinct philtrum
thin upper lip
small head, eyes, nose
brain disease related to liver cirrhosis may or may not be
related to alcohol abuse
treatment of hepatic encephalopathy
antibitoics to decr normal flora of gut
add lactuolose to acidify colon contents
hepatic encephalpathy
affects what part of brain
globus pallidus causing confusion and asterixis
chronic acquired non-wilsonian hepatocerebral degeneration = chronic hepatic encephalopathy
irrev neuro damage with chronic liver failure
destruction of neurons in deep cortex and putamen
effects of protein-caloric malnutrition
kawshiorkor
protein deficiency with edema due to
low protein
ascites
hepatomegaly with hepatic statosis
effects of protein-caloric malnutrition
caloric deficiency yields
marasmus with extreme cachexia and growth failure
–> apathy, lack of activity; effect glial formation, branching
effects of protein-caloric malnutrition
reversibility
reversible if proper nutrition restored
mechanism of B12 injury to nervous system
incorporation of abnormal fatty acids into bio membranes –> myelin instability
and NO inactiates methionine synthetase –> spinal path similar to subacute combined degeneration
subacute combined degeneration
early
late symptoms
early = sensory,
lower limb paresthesia, loss of vibration/proprioception/fine touch
late = spastic paralysis, ataxia, lower limb and trunk sensory defects
vitamin E deficiency seen when?
intestinal malabsorption cystic fibrosis celiac disease abetaliprproteinemia congenital biliary atresia
vitamin E deficiency
clinical features
acanthocytosis sensory periphery neuropathy ataxia retinopathy myopathy cardiomyopathy
vitamin E deficiency pathology
loss of dorsal root nerve cell bodies and dengeerate axons so DCML and spinocerebellar tracts affected
axonal spheroids in lower medulla
toxic leukoencephalopathy due to __
external beam irradiation and chemo for tumor
white matter damage
