Toxic Metabolic Nutritional Diseases Flashcards
Which disorders are WITHOUT morphological correlates (ie., just affect electrochemical transmission)?
x
What are the chronic affects of alcohol on the CNS?
Cerebral hemispheres may shrink via diffuse loss of white matter. Some neurons are lost from the frontal cortex with shrinking of the cell bodies, retraction of dendrites and increased lipofuscin.
Chronic alcoholism is associated with degeneration of the superior vermis of the cerebellum. The folial crests are more affected than deeper structures and includes a loss of Purkinje and granule cell neurons, plus increased number of astrocytes. Alcoholic cerebellar degeneration has specific clinical presentations that include:
• Truncal instability
• Leg ataxia
• Wide based gait
What are the acute affects of alcohol on the CNS?
Alcohol has direct effects on the cerebral hemispheres. Acute intoxication of large quantities of alcohol can cause death by central cardiorespiratory paralysis. The only finding in the brain is often cerebral edema.
What is the etiology of Wilson’s disease?
Wilson’s disease is an autosomal recessive (chromosome 13) disorder of copper metabolism. It usually presents in children or young adults. In children, the copper tends to accumulate most in the liver, leading to jaundice.
In the adults, copper is often accumulating in the CNS, especially the lentiform nucleus, causing basal ganglia degeneration and therefore leads to movement disorders (flapping tremor, spasticity, dysarthria, limb incoordination, gait disturbances, involuntary movements)
What is Wernicke’s encephalopathy?
The result of thiamine (B1) deficiency. Associated with chronic alcoholism, poor food intake, absorption problems, and increased excretion. A sudden glucose intake (often IV) can precipitate the encephalopathy
What is the etiology and pathologic findings in central pontine myelinolysis (CPM)?
Focal demyelinating lesion that preferentially involves the ventral pons. Triangular regions of demyelination with sparing of axons and neurons was seen. Clinically, most cases were too small to manifest but large lesions could cause quadriparesis, pseudobulbar palsy and pseudocoma. The etiology of this disease is the excessively rapid correction of hyponatremia which causes electrolyte imbalance in the brain and leads to edema mediated myelin destruction.
Chronic alcohol consumption + Liver damage + CNS effects =
A cirrhotic liver is unable to function normally and toxins can escape metabolism. Toxins can lead to other organ system involvement as in Hepatic Encephalopathy. The exact toxin(s) responsible for the development of encephalopathy are unknown, but ammonia is a likely candidate. Disturbances to amino acid balance may be responsible for the changes in proportion of excitatory and inhibitory neurotransmitters, or may result in false neurotransmitters.
Hepatic cirrhosis is characterized clinically by episodes of:
•confusion
•forgetfulness
•drowsiness
•eventually stupor or coma
•flapping tremor of outstretched hands (asterixis)
Histological findings include astrocytes with:
•swollen, vesicular nuclei
•little visible cytoplasm
•found in deeper cerebral cortex, globus pallidus, dentate nucleus of cerebellum and other subcortical sites
Additionally, chronic alcoholism is associated with vitamin B1 (thiamine) deficiency and the pathologic process associated with that
Clinical presentation of Wernicke’s encephalopathy
- confusion
- ataxia
- opthalmoplegia (nystagmus)
The symptoms of Wernicke’s are reversible if treated with thiamine as relatively little neuronal loss.
Pathology and imaging of Wernicke’s encephalopathy
- Mammillary bodied are almost always involved – suggestive of B1 deficiency
- Other areas of involvement: Walls of the 3rd ventricle, Periaqueductal tissue, Inferior colliculi, Floor of the 4th ventricle, Thalamus
Imaging (MRI) shows the disruption of the BBB. Acutely see loss of myelin and an influx of microglia and macrophage. Chroncially can see a loss of neurons (in addition to myelin loss), Hemosiderin, and Mammillary body atrophy
What is the etiology of Cobalamin deficiency?
Coblalmin deficiency (B12) can occur due to decreased intake (strict vegetarian/vegan), pernicious anemia, malabsorption and immune mediates atrophic gastritis. In addition to its CNS effects (addressed below), this deficiency can also cause megaloblastic anemia.
There are 2 enzymes known to require B12 in man. One of them, methionine synthetase, is important in methylation of myelin basic protein. Without proper methylation, demyelination in the nervous system occurs.
What is the treatment of Cobalamin deficiency?
IV B12 supplementation!
What are the clinical findings in Cobalamin deficiency?
Early: Ataxia, Numbness in lower extremities, Tingling in lower extremities
Parasthesias and ataxia are a result of swelling of myelin in the dorsal and lateral white matter of spinal cord, and can progress rapidly to spastic weakness or paraplegia
Other signs: Diminished vibration and proprioception, Loss of cutaneous sensation, Abnormal reflexes, Spasticity, Incontinence, Orthostatic hypotension, Dementia
What is the pathologic findings associated with Cobalamin deficiency?
- Initial lesion: spongy vacuolization of spinal cord white matter
- Myelin break down
- Macrophage influx
- Axonal degeneration
What is the pathogenesis of Wilson’s disease?
- Putamen involvement, followed by globus pallidus in CNS
- Liver accumulation of copper can lead to hepatic encephalopathy
- Neuronal loss because Cu damages neurons – perhaps by free radical generation or oxidation of membrane lipids
- Astrocytosis
- Alzeimher Type II astrocytes via Swollen vesicular nuclei andLittle cytoplasm
Treatment of Wernicke’s encephalopathy
Thiamine!
