Metabolic Diseases Flashcards

1
Q

What are two types of Metabolic Diseases?

A
  1. Genetic Metabolic Disease

2. Toxic and acquired metabolic diseases

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2
Q

What are some genetic metabolic diseases?

A
  1. Neuronal storage diseases
  2. Leukodystrophies
    - Usually show up in childhood, also called inborn errors of metabolism
    - Missing an enzyme or have low levels of it when you’re born
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3
Q

What are some toxic and acquired metabolic diseases?

A
  1. Vitamin deficiencies
  2. Metabolic and toxic disturbances
    - Things you might be exposed to , or something that you’re not getting enough of
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4
Q

What are neuronal storage diseases?

A

-Autosomal recessive enzyme deficiency
-Result: accumulation of enzyme substrate (sphinolipids, mucopolysaccharides or mucolipids) with neuronal lysosomes
-Leads to loss of cognitive function, maybe also seizures
Ex: neuronal ceroid lipofuscinoses, Tay-Sachs disease

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5
Q

-oses ?

A

means accumulation

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6
Q

What is Neuronal Ceroid Lipofuscinoses?

A
  • Deficiency of enzymes involved in protein modification/degradation
  • Lipofuscin accumulates within neurons, leading to neuronal dysfunction
  • Blindness, mental and motor deterioration, seizures
  • Onset ranges from childhood to adulthood
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7
Q

What is Tay-Sachs Disease? KNOW

A
  • Deficiency in Hexosaminidase A
  • Accumulation of ganglioside in all tissues (but nervous system shows the most symptoms)
  • Ganglioside accumulation kills the cells
  • Autosomal recessive, more common in Ashkenazi Jews
  • Usually begins in early infancy (ex: eyes aren’t tracking like they should, progresses to motor deficits)
  • Developmental delay, then paralysis and loss of neurologic function
  • Death within several years
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8
Q

What is ganglioside?

A

It is ‘food’ for a neuron.

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9
Q

What neurons are typical of storage diseases?

A

Ballooned neurons! (LARGE)

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10
Q

What do neurons look like in Tay-Sachs?

A

Show accumulation of ganglioside! Very large vacuoles filled with white material

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11
Q

What is the diagnostic clue for Tay-Sachs?

KNOW

A

“Cherry-red” spot in retina

  • Macula looks very red
  • As neurons get stuffed with ganglioside they turn whiteish/opaque - macula really stands out!
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12
Q

What are leukodystrophies?

A
  • Group of disorders characterized by myelin abnormalities
  • Most are autosomal recessive
  • Involved lysosomal or peroxisomal enzymes (DON’T NEED TO KNOW)
  • Deterioration of motor skills, spasticity, hypotonia, ataxia (Main difference btw neuronal and storage disorders)
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13
Q

What is Krabbe Disease?

A

(DON’T NEED TO KNOW)

  • Deficiency of galactosylceramidase
  • Galactocerebroside accumulates, gets converted to galactrosylsphingosine (toxic to oligodendrocytes)
  • Macrophages become very large from eating dead oligodendrocytes
  • Loss of myelin and oligodendrocytes in CNS and peripheral nerves
  • “Globoid cells” (fat macrophages) in the brain
  • Onset around 3-6 months
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14
Q

What is B1 (Thiamine Deficiency)?

A
  • Usually associated with chronic alcoholism
  • Mammillary bodies affected most
  • Wernicke encephalopathy [1st stage]
  • –Confusion, ophthalmoplegia, ataxia (gait disturbance)
  • –Hemorrhage and necrosis in mammillary bodies, walls of third and fourth ventricles
  • –Acute, reversible (at least the eye findings and ataxia, maybe not confusion)
  • Korsakoff syndrom [2nd stage - not reversible!]
  • –Memory disturbances, confabulation (story patient believes because they can’t fill a blank space in time where they blacked out - so their brain makes up a story)
  • –Cystic spaces, hemosiderin-laden macrophages in mammillary bodies, ventricle walls
  • Thalamic lesions too
  • Prolonged, mostly irreversible
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15
Q

Why do we need thiamine?

A

To make ATP, keep astrocytes working properly

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16
Q

Vitamin B12 Deficiency!

A
  • Anemia
  • –Reversibel with B12 Administration
  • Subacute combined degeneration of spinal cord
  • –Lower extremity numbness, ataxia, weakness (starts in lower legs, numbness and tingling is first symptom - reversible now but later patient will become paralyzed and it will not be reversible with B12 administration)
  • REVERSIBLE until PARAPLEGIA occurs
  • Swelling of myelin layers, vacuolization
  • Ascending and descending tracts involved
17
Q

Carbon Monoxide

A
  • Injury due to hypoxia
  • Particularly vulnerable areas:
  • –Cortex (layers II and V)
  • –Hippocampus
  • –Purkinje cells
  • May see demyelination of white matter tracts
  • CO has very high affinity for hemoglobin
  • Patient looks pink/healthy/alive when brought to the morgue
18
Q

Methanol

A
  • 30-100 mL becomes fatal (doesn’t take much to kill you -and even less to make you blind)
  • Preferentially affects retina
  • Degneration of ganglion cells
  • May cause blindness
19
Q

Ethanol

A
  • Acute effects are reversible, chronic effect are not
  • Preferentially affects cerebellum
  • Truncal ataxia (proximal muscles are more involved - had to do with damage to central part of cerebellum), unsteady gait, nystagmus (jerky eye movement)
  • Cerebellar atrophy, loss of granule cells, loss of Purkinje cells, Bergmann gloss
20
Q

What do globoid cells look like in H&E stain?

A
  • Large purple masses with some space surrounding

- Big collections of cells = macrophages filled with galactoceole

21
Q

What are the clinical symptoms of Krabbe Disease?

A
  • Muscle stiffness

- More motor in nature than other neuronal storage diseases

22
Q

What does the brain of someone with Wernicke encephalopathy look like?

A

Dark black hemorrhages are shown in the mammillary bodies - almost more like Korsakoff syndrome and probably not reversible at this point

23
Q

What happens on a cellular level with wrench encephalopathy?

A

Atrophy of mammillary bodies

24
Q

What happens in subacute combined degeneration of the spinal cord in Vitamin B12 deficiency?

A
  • Nate’s dad takes VB12 and he never drinks
  • Subacute combined degeneration
  • Disease begins to demyelinate axon tracts and you can see this in the H & E slide of the spinal cord
25
Q

What can happen in chronic alcoholism/ethanol over exposure?

A
  • Cerebellar atrophy

- Loss of purkinje cells

26
Q

What is bergmann gliosis?

A
  • Ethanol induced
  • Shows two thick pink lines on H & E stain
  • Many astrocytes are collecting where purkinje cells are reacting/changing
  • Astocytes proliferating!