Psychiatry Pathology Flashcards
Alzheimer’s pathophysiology of plaques
Normal Physiology
Amyloid pre-curser protein ( APP)–> grows and repairs neurone after injury. Normally recycled by two enzymes ( alpha secretase and gamma secretase ) which cuts extracellular segment of APP to make it water soluble .
When things go wrong :
Gamma secretase pairs with BETA secretase causing the protein that was cut to be INSOLUBLE= AMYLOID BETA = sticky and together to form beta amyloid plaques
Plaques get in between neurons = interfere with signalling , so memory is impaired
Inflammation damages neurones
Around blood vessels : Amyloid Angiopathy which weakens walls of the blood vessels => haemorrhage
Alzheimers pathophysiology of tangles
Tangles are found inside the neurones
Microtubules make the cytoskeleton. They are held together by protein called TAU
KINASE is an enzyme which transfers phosphate to the TAU protein
This leads to a conformational change causing the TAU proteins to get tangled –> Alzheimer’s disease
Non- functioning microtubules –> casue apoptosis of neurones
This leads to the atrophy (shrinks) of the brain
Gyri get smaller and sulci get larger
Ventricles get larger
Dementia diagnosis?
History -impact on daily life -talk to family members too -Physical & neurological examination Undertake appropriate blood (FBC’s, ESR, CRP) and urine tests: Use cognitive testing. -CT used to measure vascular damage
Dementia treatment
Pharmacological management : do not stop/slow down the neurodegenerative progress but help with symptom relief
1) Acetycholinesterase inhibitors: donepezil, galantamine and rivastigmine as monotherapies (increases ACH levels)
2) NMDA receptor antagonist (Memantine) ( limits ca2+ influx , which prevents the cell rupturing and dying)
what is Parkinsonism ? What is Parkisons?
1) Hypertonia, tremor, bradykinesia ( slow movement that progressively get SLOWER)
- due to drugs or cerebrovascular disease,e
- CO poisoning
- post encephalitic
2)Parkinsons –>idiopathic , impaired function of dopaminergic neurones projecting from the substantia nigra to corpus striatum
Types of amyloidosis , how are they classified ?
They can be classified according to the protein they affect ie : most prevalent :
Myeloma associated = AL immunoglobulin light chains of fragments affected
Reactive amyloidosis = AA = Amyloid protein A
Alzheimer’s = A-beta derived from APP
Amyloid stains positive with Congo red, and shows apple green birefringence in polarised light !
Lewy body dementia, what are the plaques made of ? Symptoms ?
Plaques made of alpha-synuclein , build up everywhere –> cerebral cortex, limbic system
Parkinsons is associated with these bodies in the substantial nigra
Bizzare behaviour :
Parkinsonism and fluctuations in cognitive impairment and visual hallucinations, often before Parkinsonian features occur.
what is chronic traumatic encephalopathy
Punch drunk syndrome ie : Muhammed Ali
- neurobehavioural dysregulation
- affects every part of the Brain
what are prion diseases ?
example?
sporadic vs variant ?
Creutzfeldt-Jakob disease (CJD) describes a group of neuro-degenerative diseases caused by prions (mis-shaped proteins).
- Protein + inflammation
- spongiform changes in cerebral cortex
Sporadic vs variant= MRI
- > Variant CJD there is changes including high signal in the posterior thalamus (has high sensitivity and specificity).
- > Sporadic CJD there is increased intensity in the caudate and putamen
Huntingdons disease
symptoms genetic info ?
- Autosomal dominant Trinucleotide repeat disorder = CAG
- Caudate nucleus and putamen especially affected
- widening of lateral ventricles
- Genetic anticipation => the next generation will be affected earlier
Symptoms:
Dominant inheritance
Choreoathetosis ( movement disorder caused by underlying causes)
Dementia
what is chorea
causes
treatment
Think choreography
- dancing arms and legs ( rapid jerky movement)
Number one cause is Huntington’s disease, Levodopa can also cause chorea
Treatment is : dopamine receptor blockers = tetrabenazine
what is a Hemiballismus
SEVERE PROXIMAL CHOREA = violent swinging movement
Causes: VASCULAR CAUSES
- infarction
- haemorrhage in contralateral subthalamic nucleus
treatment= dopamine blockers
TICS
Sudden, repetitive non -rhythmic stereotyped movement
- Conscioussly choose to release relieving urge
- suppressible BUT Irresistable ( increases in stress and excitement )
1) Motor tics
2) Vocal tics
Causes:
- simple transient tics in childhood
- tourettes
- neurodegenerative disease (Wilsons)
- LDs
Tourettes
- treatment
Severe tic disorder , has to be diagnosed before the age of 18 ( more common in boys)
- multiple motor and at least one vocal tic
Treatment : psychobehavioural therapy
Myoclonus
irregular fast jerk ( like tremor but not rhythmic )
drug induced Dyskinesias
tremor = salbutamol , lithium , Valproate Dyskinesia= levodopa
Tardive dyskinesia = lip smacking, grimacing and contortion of the face and neck => due to neuroleptic , anti psychotic drugs
what is tardive dyskinesia ?
what is it due to ?
Tardive dyskinesia = lip smacking, grimacing and contortion of the face and neck => due to neuroleptic , anti psychotic drugs
*Temporal lobe seizure would also cause lip smacking
whats Athetosis ?
- involuntary SLOW writhing movements
- exaggerated posture of the limbs
- due to birth trauma / cerebral palsy
what is Wilsons disease ?
BUILD UP OF COPPER IN BRAIN, LIVER AND CORNEA mixed movement disorder - wing beating tremor - dystonia - Chorea
Autosomal recessive inheritance
treatment = copper absorbing drugs = penicillamine , trietene
whats ataxia
Ataxia is a term for a group of disorders that affect co-ordination, balance and speech.
Any part of the body can be affected, but people with ataxia often have difficulties with: balance and walking. speaking. swallowing.
what is cerebellar ataxia
-Disorder that occurs when the cerebellum becomes inflamed or damaged.
- The cerebellum is the area of the brain responsible for controlling gait and muscle coordination. The term ataxia refers to a lack of fine control of voluntary movements
(past pointing , head tremor, gait ataxia, intention tremor )
- they are limb movements ( Ipsilateral side of the brain)
does stroke affect the same side or different side of the body ?
- contralateral Side of body
right sided stroke is left side of the body
what is a tremor ?
what kind of tremors can we have ?
causes of tremor ?
- involuntary , rhythmic , oscillatory movement of body part
1) resting tremor
2) Action tremor
causes : - essential tremor
-drug induced
-degenerative disorders
-metabolic diseases
-peripheral neuropathies
-toxins
