Lecture 23 Flashcards
Disorders of development (toxins)
Doxins during gestation have impacts on kids
Organophosphates and heavy metals
Alcohol
Cigarettes
Fetal alcohol syndrome
Alcohol consumption heavily in the 3rd and 4th week of pregnancy
Facial anomalies and cognitive disabilities
Alcohol consumption outside of this window is also damaging in proportion to the amount of alcohol consumed
Inherited metabolic disorders
Errors of metabolism caused by a defect in protein. Often an enzyme is not made as a result
Phenylketonuria (PKU)
Absence of enzyme that converts phenylanine to tyrosine
phenylanine accumulates and causes brain damage
restrictive diet which excludes all of this can stop it
Tay-Sachs disease
Heritable
Was common in southern QC for hundreds of years
Lack of enzymes in lysosomes causes accumulation of waste large lysosomes, cell death and swelling of brain
Downs syndrome
Extra 21st chromosome
Congenital - not always hereditary (though the kid of downs has 50% shot)
usually an error in meiosis
Moderate to serious intellectual disabilities. Mixed because you do not know what genes will be inactivated
At age 30 - degenerates like Alzheimer’s sufferer
Alz can be coded fror by genes on 21 chrom. As it has more 21 chrom = more disease.
Encephalitis and Menigitis
Encephalitis is inflammation of the brain by infection, toxic chemicals or allergy
Headache, fever and nausea
Meningitis - inflammation of meninges caused by fever and nausea
Headache and stiff neck
Polio
Acute anterior poliomyelitis Viral disease that destroys motor neurons of the brain and spine Makes copies of itself in motor neurons They die 1% get it into the brain 10% of these are paralyzed
Rabies
Fatal viral disease
Retrograde virus
Time left to give vaccine varies by where bitten as it must travel up the nerves to the brain
Herpes simples
Rarely, enters brain and causes encephalitis
Multiple Sclerosis
Autoimmune
Has some gene factors but often sporadic
Demyelinates
LEaves hard patches, sclerotic plaques
Normal transmission interrupted as channels only exist on nodes of R and so AP is not propagated properly
Many symptoms as widespread and hetrogeneous
Usually remitting-relapsing
Interfearon beta modulates immune response
Glatiramer acetate mimics myelin so is a decoy
Dont work well
More common father from the equator so probably a disease common there contributes
Athelrosclerosis
Linings of arteries develop plaque of dats and waste products
Risk factors high BP, cigarettes, diabetes, high cholesterol
Precursor to MI and strokes
Common in interior carotid artery
Can be seen on angiogram
Stroke types
Hemorrhagic
Rupture of a cerebral blood vessel
Ischemic
Occlusion
87%
Strokes Thrombus/embolus
Thrombus is a clot that forms in a blood vessel and may block it
Embolus breaks off and imbeds itself later in blood vessel - in brain = stroke
Can be negligible or massive depending on size and location
Can cause perm brain damage but with therapy can produce large improvements
Anti clot stuff can work like tPA (tissue plasminogen activator) if its 3-4 hours after stroke
Tumors
Non malignant - benign
Distinct border, cannot metastasize
Malignant, no clear border can move
Often depends on whether it is encapsulated or not. If so, sugeon can often remove it
If it infiltratesm much hardewr.
If surgeon misses a cell, comes back
In brain - compression and infiltration
Compression can directly destroy brain or block CSF causing hydrocephalus
Gliomas
Malignant
Glial cells
Very low survival
Meningioma
Non malignant
Often between hemispheres
Meningeal cells
Not necessarily benign if you do not go to doctor and people put it off cos its slow and they assume ok
Degenerative disease basics
Caused by apoptosis due to build up of some form of protein
Prions
Malformed proteins, edit other malformed proteins into them and then aggregate
Transmissible spongiform encephalopathy
Includes mad cow
Gives spongy appearance to brain
Prion accumulation causes this
Prions are the only infective agents that are just a protein
Huntington’s
1 in 10000
Dominant
30-50 years old
Excess movement, dementia, death
Caused by a build up of protein hungtingtin
Has over 39 glutamines
As generation persist, this chain gets longer so spontaneously reemerges.
Enzyme attaches and slips off, reattaches at wrong place
Makes hungtingtin protein
Heavily expressed in basal ganglia
Antisense DNA administered in spinal canal intrathecally
binds to huntingtin rna and stops translation
Clumps up and kills cells
Antisense gene therapy might work
Parkinson’s
1%
over 60
Shaking, dementia
Part gene part environment, mostly unknown
Alpha-synuclein is expressed in dopamine and clumps together. With time, causes these cells to die
Aggregates are called Lewy bodies
Mutation that causes this can be dominant
When proteins form wrong, the protein Parkin adds an Ubiquitin to them. Ubiquitinated proteins are destroyed by proteasomes. If parkin is inactive, does not happen. This causes alpha-synuclein to accumulate
Parkinson’s gain/loss of fx
Hunti parki
Toxic gain of fx
Dominant
Mutations in huntingtin or alpha-synuclein gene
cause Huntington’s and Parkinson’s
LOSS of fx
Recessive
Parkin does not work
Parkinson’s
Parkinson’s treatment
While there are still dopaminergic neurons left
Give L dopa to increase their output
When this fails, implant electrodes and do high f deep brain stimulation DBS
Target subthalamic nucleus, initially 130hs
Shuts it off and movement issues go away
Eventually the system adapts and stops working so you have to increase simulation frequency
Patients can control by remote
Better than old way of lesioning Globus pallidus or subthalamic nucleus as reversible
