Psychiatry Pathology

Question 1

Alzheimer’s pathophysiology of plaques

Answer 1

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

Question 2

Alzheimers pathophysiology of tangles

Answer 2

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

Question 3

Dementia diagnosis?

Answer 3

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

Question 4

Dementia treatment

Answer 4

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) ​

Question 5

what is Parkinsonism ? What is Parkisons?

Answer 5

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

Question 6

Types of amyloidosis , how are they classified ?

Answer 6

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 !

Question 7

Lewy body dementia, what are the plaques made of ? Symptoms ?

Answer 7

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.

Question 8

what is chronic traumatic encephalopathy

Answer 8

Punch drunk syndrome ie : Muhammed Ali

• neurobehavioural dysregulation
• affects every part of the Brain

Question 9

what are prion diseases ?
example?
sporadic vs variant ?

Answer 9

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

Question 10

Huntingdons disease

symptoms genetic info ?

Answer 10

• 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

Question 11

what is chorea

causes

treatment

Answer 11

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

Question 12

what is a Hemiballismus

Answer 12

SEVERE PROXIMAL CHOREA = violent swinging movement

Causes: VASCULAR CAUSES

• infarction
• haemorrhage in contralateral subthalamic nucleus

treatment= dopamine blockers

Question 13

TICS

Answer 13

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

Question 14

Tourettes

- treatment

Answer 14

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

Question 15

Myoclonus

Answer 15

irregular fast jerk ( like tremor but not rhythmic )

Question 16

drug induced Dyskinesias

Answer 16

tremor = salbutamol , lithium , Valproate 
Dyskinesia=  levodopa 

Tardive dyskinesia = lip smacking, grimacing and contortion of the face and neck => due to neuroleptic , anti psychotic drugs

Question 17

what is tardive dyskinesia ?

what is it due to ?

Answer 17

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

Question 18

whats Athetosis ?

Answer 18

• involuntary SLOW writhing movements
• exaggerated posture of the limbs
• due to birth trauma / cerebral palsy

Question 19

what is Wilsons disease ?

Answer 19

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

Question 20

whats ataxia

Answer 20

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.

Question 21

what is cerebellar ataxia

Answer 21

-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)

Question 22

does stroke affect the same side or different side of the body ?

Answer 22

• contralateral Side of body

right sided stroke is left side of the body

Question 23

what is a tremor ?
what kind of tremors can we have ?
causes of tremor ?

Answer 23

• 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