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Week 5 Flashcards

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1
Q

Describe the Molecular theory of aging

A

Age related genetic regulation by epigenetic modifications
Gene methylation
Histone modification
Accumulations of mutations

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2
Q

Describe the Cellular theory of aging

A

Telomere shortening - progressive loss of chromosome “caps”
Free radical damage to DNA
Apoptosis

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3
Q

Describe the Environmental and Evolutionary theory of aging

A

“Wear and tear” - inability to regenerate damaged tissue
Cumulative UV and ionising radiation damage
“Disposable soma” ie no evolutionary advantage in survival beyond reproduction and child rearing

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4
Q

What is Frailty?

A

A clinically recognisable state of increased vulnerability resulting from aging - associated decline in reserve and function across multiple physiologic systems such that the ability to cope with everyday or acute stressors is comprised

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5
Q

What are the 3 phenotypes of Frailty?

A

Robust
Pre-Frailty
Frailty

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6
Q

What is the leading cause of sight impairment in the UK?

A

Age-related macular degeneration

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7
Q

What are some risk factors for Corneal Ulcers?

A

—Contact lenses—
Herpes
Steroid drop use
Dry eyes

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8
Q

What are some risk factors for Cataracts?

A

—Age—
Diabetes
Trauma
Inflammation

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9
Q

What may cause an abnormal retinal reflex?

A

Anything obstructing the path of light from front to back of eye

Corneal scar
Cataract
Vitreous Haemorrhage
—Retinoblastoma—

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10
Q

What is the “2-hit” hypothesis in relation to Retinoblastoma?

A

The RB1 gene if damaged hereditarily will lead to bi lateral and early presentation

Non-hereditary with “2-hits” to the RB1 gene will be unilateral and present later

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11
Q

Describe Diabetic Retinopathy

A

Reduced vision due to:
Growth of new vessels, Vitreous haemorrhage, tractional retinal detachment and rubeotic glaucoma
Leakage of fluid from damaged vessels; Macular oedema w/ loss of central visual acuity

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12
Q

Describe Retinopathy of prematurity

A

Retinopathy due to early birth not giving enough time for the eyes blood vessels to develop

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13
Q

What are the 2 types of Age-related Macular Degeneration and which one can’t really be directly treated

A

Dry and Wet
Dry can’t be directly treated

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14
Q

How do we treat WET age-related macular degeneration?

A

Inject anti-VEGF

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15
Q

What are some causes of swollen discs?

A

Raised ICP
Space occupying lesion (brain tumour)
Hydrocephalus

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16
Q

What is the main sign of Glaucoma?

A

Cupped disc

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17
Q

What is Glaucoma most commonly associated with?

A

Raised intra ocular pressure (IOP)

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18
Q

What are some symptoms of a 3rd CN Palsy?

A

Vertical diplopia
Eye is “down and out”
Pupil dilated and ptosis
May be due to aneurysm

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19
Q

What are some symptoms of a 4th CN Palsy?

A

Oblique diplopia
Head tilt away from side of lesion
Diplopia on adduction
Common after head injury

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20
Q

What are some symptoms of 4th CN Palsy?

A

Horizontal diplopia
Worse in far distance
Worse toward side of palsy if unilateral
Bilateral - concerned about raised ICP

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21
Q

Define dementia

A

General term for loss of memory, language, problem-solving and other thinking abilities

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22
Q

What are some risk factors for dementia?

A

Sex
Ethnicity
Genetics
Amount of Cognitive reserve
Lifestyle choices

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23
Q

What are some symptoms of Early stage Alzheimer’s disease?

A

Loss of memory of recent events
Poor orientation
Difficulties concentrating and planning
Language
Mood

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24
Q

What are some symptoms of Middle stage Alzheimer’s disease?

A

Worsening memory problems
Difficulties toileting (soiling selves)
Difficulty recognising people

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25
What are some symptoms of Late stage Alzheimer's disease?
Severe memory difficulties Significant problem recognising faces Communication can be very difficult Behavioural changes Psychosis
26
What may the patient experience upon being diagnosed with Dementia?
Shock Relief (know cause of symptoms) Disbelief Anxiety Fear, Grief, Hopelessness
27
What is the difference between a benign and malignant tumour?
Benign is non-invasive where as malignant is invasive
28
The most common tumours in the brain are what?
Metastatic
29
What may be some symptoms of a space occupying lesions?
Fits Visual Drowsiness Behavioural changes
30
What specific kinds of Lung cancer may metastasize to the brain?
- Small cell undifferentiated - Squamous - Adeno
31
What kinds of cancer may metastasize to brain?
Lung Breast Gastric Colorectum
32
What are Meningioma's?
At sites of arachnoid matter Grossly, well demarcated Slow growing Non invasive, but erosive and compressive
33
What are some symptoms and treatment for Meningioma's?
Fits, Drowsiness, Headaches Surgical removal
34
What are the subtypes of Glioma's?
Astrocytomas Oligodendroglioma Ependymoma Choroid plexus tumours
35
What is an issue with treating Glioma's?
Present so late that by the time you're aware of them, surgical removal is no longer viable Have to use radiotherapy
36
Are Glioma's always Benign, or always Malignant?
Always Malignant
37
When diagnosing different types of Glioma's, what may be used to help tell what kind of Glioma it is?
Molecular genetic testing
38
What are some Peripheral nerve tumours?
Schwannoma Neurofibroma Neural - Neuroblastoma, Ganglioneuroma
39
Where are schwannomas?
Myelinating Schwann cells Outside neuron, within perineural sheath pressing on nerves
40
Where are Neurofibroma’s?
Grow on the nerve
41
Describe Neurofibromatosis 1
Autosomal Dominant 50% Spontaneous
42
Describe Neurofibromatosis 2
Bilateral acoustic Schwannoma
43
What actually happens structurally to the brain as a result of Huntington's disease?
Atrophy of Caudate nuc. and Putamen
44
What are the issues with altered Polyglutamine in Huntington's disease?
Protein misfolds Aggregates Inclusion bodies
45
Describe fragile X syndrome
Single gene disorder on the X chromosome 1/4000 males 1/8000 females
46
Describe some symptoms of Fragile-X phenotype
Long face Mitral valve prolapse Learning difficulties ADD Autistic like behaviour
47
What issue of the gene leads to Fragile X syndrome?
Trinucleotide repeat in 5' non-coding region
48
What is the function of FMR1 protein?
Highly expressed in neurons Regulates mRNA translation in dendrites
49
What are 3 main examples of trinucleotide repeat diseases?
Huntington's Fragile X Myotonic Dystrophy
50
What are two signs on the cellular level for Alzheimer's disease?
Extracellular Plaques of Beta amyloid Intracellular Tangles of hyperphosphorylated Tau proteins
51
Describe what happens in abnormal function of Amyloid precursor protein (APP)
Cleavage of APP creates Amyloid beta peptides that form oligomer aggregates
51
Mutations in what are associated with early onset Alzheimer's disease?
Presenilin 1 and 2 Affect activity of gamma-secretase
52
Describe function of ApoE
Cholesterol transport Clears amyloid beta
53
What are the 3 alleles of ApoE?
E2, E3 and E4
54
What is the relation between the alleles of ApoE and Alzheimer's diseaes?
Heterozygotes for E4 have 4 fold risk Homozygotes for E4 have 15 fold risk
55
What is the function of Tau protein?
Binds and stabilises microtubules (in neurons)
56
Describe Prion Diseases
Transmissible spongiform encephalopathy
57
What are 3 examples of Prion diseases?
Creutzfeld-Jakob disease Fatal familial insomnia Kuru
58
Describe a Prion
Proteinaceous Infectious Carries no genetic material
59
What forms of therapy can be used for Prions?
Stabilising PrP^C conformation Clearance of PrP^SC Vaccination against PrP^SC
60
What are the 2 muscles responsible for accommodation of pupil?
Dilator pupillae Sphincter pupillae
61
With asymmetrical pupils, what may cause larger pupils?
3rd nerve palsy Sphincter damage Drugs
62
With asymmetrical pupils, what may cause smaller pupils?
Horner's syndrome Uveitis Drugs
63
What is the main sign of Glaucoma, and what is it often associated with?
Cupping Raised intraocular pressure
64
What layers of the Lat. Geniculate nuc. receive ipsilateral and contralateral?
Ips. - 2, 3, 5 Cont. - 1, 4, 6
65
Describe Magnocellular ggl. cells
Large axons (lots of myelin) Fast Receive info from large no. of photoreceptors Movement, brightness, depth perception Project to parietal lobes
66
Describe Parvocellular ggl. cells
Thin axons (less myelin) Slow Receive info from small no. of photoreceptors Detail of objects assisting in recognition Project to temporal lobes
67
What is the function of the Occipital lobe?
Relay station Retinotopic map Neural tuning responds to: 1. colour 2. spatial frequency 3. orientation
68
What is the most common cause of Amblyopia?
Uncorrected refractive error in ONE eye
69
What are some treatments for Amyblyopia?
Patching Glasses Corrected squint
70
What eye issues may lead to a retinal lesion?
AMD Diabetic eye disease Retinal detachment
71
What issues may lead to a Chiasmal lesion?
Pituitary tumour Craniopharyngioma
72
What issues may lead to post Chiasmal lesions?
Stroke Space occupying lesions (Tumours + Bleeds)
73
What are the two separate functional streams of visual information?
'What' and 'Where'
74
Give some examples of common Motor neuron diseases
-Amyotrophic Lateral Sclerosis (ALS) -Progressive Bulbar Atrophy -Primary Lateral Sclerosis -Spinal Muscular Atrophy
75
What makes up a Motor Unit?
Motor neurons and group of innervated muscle fibres
76
What are the 4 types of Motor Unit Disorders?
- Motor Neuron Disease - Peripheral Neuropathies - Diseases of the NMJ - Primary Muscle Disease
77
How would the origins of 90% of ALS cases be described?
Sporadic
78
Describe ALS
Disease is linked with loss of LMNs in both the Bulbar and spinal cord, and in the UMN, spinal cord, brainstem and the cortex Leads to cramps and weakness on one side followed by the other Ultimately patient can't breathe and dies
79
What are some signs of ALS?
Focal weakness and clumsiness Painful fasciculations / cramps UMN and LMN signs Dysarthria, Dysphasia or respiratory issues
80
What often degenerates in ALS?
Corticospinal tracts (B - mild C - severe)
81
Describe the pathology of Alzheimer's disease
65+ y/o Neuronal cell death in Entorhinal cortex and Hippocampus Cortical atrophy Amyloid plaques + hyperphosphorylated tau
82
What percentage of Alzheimer's disease are Sporadic or Familiar
Sporadic - 90% Familiar - 10%
83
What is Braak staging?
Pathological, post-mortem assessment of tau neurofibrillary and beta-amyloid progression based on brain anatomical distribution
84
Describe the pathology of Parkinson's disease
Neuronal loss in substantia nigra degeneration of nigrostriatal tract Profound loss of dopamine in basal nuc.
85
Describe Prion disease in spongiform Encephalopathies
Caused by a misfolded cell surface protein - causes cells and proteins to clump together resulting in death Most common form is Creutzfeldt-Jakob disease (CJD)
86
What are the 3 types of CJD (Creutzfeldt-Jakob disease)?
Familial Sporadic Acquired
87
What are some symptoms of CJD?
Rapidly developing dementia Difficulty walking Muscle stiffness and fatigue Speech problems
88
Describe Multiple Sclerosis
Autoimmune disease of CNS Immune cells phagocytose myelin Signal transmission is slowed Proprioceptive info doesn't synchronise w/ motor output Muscle fatigues and patients find it difficult to control movement
89
What are some clinical presentations of MS?
Depends on area affected: Optic Nerve - visual field Corticobulbar - speech swallowing Corticospinal - muscles strength Cerebellar - gait coordination Spinocerebellar - balance
90
Give some examples of Inherited muscle diseases
- Dystrophies - Congenital myopathies - Metabolic - Myotonic
91
Give some examples of acquired muscle diseases
Inflammatory Toxic (alcohol) Metabolic Disuse atrophy
92
Describe Duchenne Muscular Dystrophy
X-linked recessive trait that affect male in early childhood Mutation in DMD gene
93
Describe the clinical presentation of DMD (Duchenne Muscular Dystrophy)
Onset 3-5 years Muscle weakness begins in pelvic girdle and progresses to shoulders Cardiac muscle damage and fibrosis High serum level of creatine kinase at birth and childhood
94
Glioma Grading
95
What is needed before you get Abeta deposition in Alzheimer's?
Both APP mutation and PSEN1/2 mutation Activates both **beta** and **gamma secretase** enzymes respectively

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