Toxic Metabolic Disorders - DeMasters Flashcards
What can ingestion of methanol cause (besides blindness)?
Hemorrhagic necrosis in the putamen.
What is the risk of acute alcohol intoxication?
Cerebral edema.
What is seen in chronic alcoholism? What 2 regions are affected? What cell types are affected (histology)?
Cerebral atrophy (white matter, particularly) Cerebellar atrophy (Superior vermis is vulnerable to chronic alcoholic damage. There may be some correlation with vitamin deficiency. Loss of purkinje and granular cell neurons)
Withdrawal (delirium tremens)
What can characterize FAS (Fetal Alcohol Syndrome)?
Features include hyperactivity, poor motor skills, learning difficulties; severely affected kids have mental retardation
Facial features (very severe only): small midface, small head, thin upper lip with indistinct philthrum, skin folds at corner of the eye, low nasal bridge.
What neurologic complications can be seen as a result of chronic alcohol abuse due to cirrhosis?
What are the symptoms?
What are the histological features?
What is the metabolic pathway in the brain that causes symptoms?
“Chronic acquired nonwilsonian heptaocerebral degeneration.”
Ammonia is produced by protein catabolism and gut bacteria. Hepatic encephalopathy–> rising levels of ammonia due to failure of liver to convert to urea (congestion can bypass liver). Tx is avoidance of protein + antibiotics.
Symptoms are global confusion and asterixis [Asterixis – press on the hand and it vibrates. basal ganglia (particularly globus pallidus) is responsible for smooth movements.]
Glutamine synthase in the astrocyte uses NH4 to create glutamate. The development of astrocytes with swollen, vesicular nuclei and little visible cytoplasm called “Alzheimer type II” astrocytes is seen especially in deeper cerebral cortex, globus pallidus, dentate nucleus of the cerebellum, and other subcortical sites.
What causes Wilson’s disease?
What are the signs and symptoms?
Wilson’s disease is an inherited condition that prevents the metabolism of copper. The neuropathology is not due directly to copper, but rather to repeated bouts of hepatic encephalopathy that occur during disease course.
The clinical presentation manifests with the same signs and symptoms as non-wilsonian HE, as well as jaundice in children or a movement disorder in adults.
What is thiamine? What is a thiamine deficiency called (Eponym). IN what population is it most common?
What are the signs/symptoms?
What areas or the brain are affected? Is it fatal?
Vitamin B1. Wernicke’s syndrome/encephalopathy. Mostly seen in alcoholics. Can also see in hyperemesis.
Signs are visual disturbances, nystagmus, ataxia, confusion. People also confabulate wildly.
Affects the mammillary bodies (edema, necrosis). WE CAN SEE THIS ON MRI so it will be on the test (axial scan, see bright signal centrally between the ventricles in the thalami.
Can die from petechial hemorrhages in the hypothalamus.
Describe in detail the metabolic pathogenesis of Wernicke’s encephalopathy and how it leads to irreversible brain damage.
Thymine deficiency–> alpha ketoglutarate dehydrogenase complex (aKDGH) shuts down–> starts fgiving off NO–> glutamate gradient changes (high ECF, low ICF)–> osmotic gradients disrupted–> Edema –> BBB breakdown–> increased lactate and acidosis in neurons–> necrosis and irreversible damage
Describe the basics of B12 absorption. Where is it found in diet, where is it absorbed, what events most frequently lead to deficiency?
What is another name for B12? What is another name for the neurologic condition caused by insufficient B12?
B12 (aka Cobalamin) binds to Intrinsic Factor (parietal cells of the stomach produce this) and is absorbed in the terminal ileum.
It is a fat-soluble vitamin so body stores can last years (3-4) before becoming deficient.
B12 is found in meat and dairy, so strict vegans can become deficient. People who make autoantibodies against IF can also succumb (This is termed atrophic gastritis).
SCD - Subacute Combined Degeneration
What causes symptoms/disease in B12 deficiency?
What substance, when abused, can mimic B12 deficiency?
Two enzymes require B12: methionine synthetase and methylmalonyl CoA mutase.
Dysfunction of these enzymes may cause incorporation of abnormal fatty acids into biological membranes, resulting in myelin instability.
nitrous oxide recreational abuse/use inactivates methionine synthetase and causes spinal cord pathology identical to SCD
What are the clinical manifestations of cobalamin deficiency?
Compare/contrast early and late signs of Subacute Combined Degeneration (SCD). What area of the spinal column is affected?
Does tx reverse these effects?
Megaloblastic anemia and/or neurologic deficits.
Early: lower limb paresthesias, loss of proprioception
Late: spastic paraparesis, ataxia, lower limb and sensory defects
Spinal column: Dorsal and lateral tracts affected.
Treatment is effective in reversing disease course unless very severe/prolonged.
What is kwashiorkor?
Protein deficiency yields kwashiorkor with edema due to hypoproteinemia, ascites, hepatomegaly with hepatic steatosis (fatty liver). Brain will show loss in volume. No specific gross/microscopic abnormality. With restoration of proper nutrition, the child can recover, in part due to childhood neuronal synapse formation and white matter formation.
What condition occurs when someone’s hyponatremia is overcorrected, or corrected to rapidly?
Central Pontine Myelinolysis. Triangular areas of demyelination with relative sparing of the axons and neurons were seen. In more severe cases extrapontine lesions found.
The disease preferentially involves the ventral pons. The close admixture of grey and white matter in this site may lead to edema mediated myelin damage resulting from osmotic opening of the blood brain barrier
Disease affects an area not affected by much else. In people with severe CPM, you would end up with bad symptoms centering in these areas (basilar pons).
Can lead to locked-in syndrome (eg complete degeneration of the motor tracts). Visible on gross and microscopic histology.
Largely a historical disease.
