Week 5 Flashcards
Describe the Molecular theory of aging
Age related genetic regulation by epigenetic modifications
Gene methylation
Histone modification
Accumulations of mutations
Describe the Cellular theory of aging
Telomere shortening - progressive loss of chromosome “caps”
Free radical damage to DNA
Apoptosis
Describe the Environmental and Evolutionary theory of aging
“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
What is Frailty?
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
What are the 3 phenotypes of Frailty?
Robust
Pre-Frailty
Frailty
What is the leading cause of sight impairment in the UK?
Age-related macular degeneration
What are some risk factors for Corneal Ulcers?
—Contact lenses—
Herpes
Steroid drop use
Dry eyes
What are some risk factors for Cataracts?
—Age—
Diabetes
Trauma
Inflammation
What may cause an abnormal retinal reflex?
Anything obstructing the path of light from front to back of eye
Corneal scar
Cataract
Vitreous Haemorrhage
—Retinoblastoma—
What is the “2-hit” hypothesis in relation to Retinoblastoma?
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
Describe Diabetic Retinopathy
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
Describe Retinopathy of prematurity
Retinopathy due to early birth not giving enough time for the eyes blood vessels to develop
What are the 2 types of Age-related Macular Degeneration and which one can’t really be directly treated
Dry and Wet
Dry can’t be directly treated
How do we treat WET age-related macular degeneration?
Inject anti-VEGF
What are some causes of swollen discs?
Raised ICP
Space occupying lesion (brain tumour)
Hydrocephalus
What is the main sign of Glaucoma?
Cupped disc
What is Glaucoma most commonly associated with?
Raised intra ocular pressure (IOP)
What are some symptoms of a 3rd CN Palsy?
Vertical diplopia
Eye is “down and out”
Pupil dilated and ptosis
May be due to aneurysm
What are some symptoms of a 4th CN Palsy?
Oblique diplopia
Head tilt away from side of lesion
Diplopia on adduction
Common after head injury
What are some symptoms of 4th CN Palsy?
Horizontal diplopia
Worse in far distance
Worse toward side of palsy if unilateral
Bilateral - concerned about raised ICP
Define dementia
General term for loss of memory, language, problem-solving and other thinking abilities
What are some risk factors for dementia?
Sex
Ethnicity
Genetics
Amount of Cognitive reserve
Lifestyle choices
What are some symptoms of Early stage Alzheimer’s disease?
Loss of memory of recent events
Poor orientation
Difficulties concentrating and planning
Language
Mood
What are some symptoms of Middle stage Alzheimer’s disease?
Worsening memory problems
Difficulties toileting (soiling selves)
Difficulty recognising people
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
What may the patient experience upon being diagnosed with Dementia?
Shock
Relief (know cause of symptoms)
Disbelief
Anxiety
Fear, Grief, Hopelessness
What is the difference between a benign and malignant tumour?
Benign is non-invasive where as malignant is invasive
The most common tumours in the brain are what?
Metastatic
What may be some symptoms of a space occupying lesions?
Fits
Visual
Drowsiness
Behavioural changes
What specific kinds of Lung cancer may metastasize to the brain?
- Small cell undifferentiated
- Squamous
- Adeno
What kinds of cancer may metastasize to brain?
Lung
Breast
Gastric
Colorectum
What are Meningioma’s?
At sites of arachnoid matter
Grossly, well demarcated
Slow growing
Non invasive, but erosive and compressive
What are some symptoms and treatment for Meningioma’s?
Fits, Drowsiness, Headaches
Surgical removal
What are the subtypes of Glioma’s?
Astrocytomas
Oligodendroglioma
Ependymoma
Choroid plexus tumours
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
Are Glioma’s always Benign, or always Malignant?
Always Malignant
When diagnosing different types of Glioma’s, what may be used to help tell what kind of Glioma it is?
Molecular genetic testing
What are some Peripheral nerve tumours?
Schwannoma
Neurofibroma
Neural - Neuroblastoma, Ganglioneuroma
Where are schwannomas?
Myelinating Schwann cells
Outside neuron, within perineural sheath pressing on nerves
Where are Neurofibroma’s?
Grow on the nerve
Describe Neurofibromatosis 1
Autosomal Dominant
50% Spontaneous
Describe Neurofibromatosis 2
Bilateral acoustic Schwannoma
What actually happens structurally to the brain as a result of Huntington’s disease?
Atrophy of Caudate nuc. and Putamen
What are the issues with altered Polyglutamine in Huntington’s disease?
Protein misfolds
Aggregates
Inclusion bodies
Describe fragile X syndrome
Single gene disorder on the X chromosome
1/4000 males
1/8000 females
Describe some symptoms of Fragile-X phenotype
Long face
Mitral valve prolapse
Learning difficulties
ADD
Autistic like behaviour
What issue of the gene leads to Fragile X syndrome?
Trinucleotide repeat in 5’ non-coding region
What is the function of FMR1 protein?
Highly expressed in neurons
Regulates mRNA translation in dendrites
What are 3 main examples of trinucleotide repeat diseases?
Huntington’s
Fragile X
Myotonic Dystrophy
What are two signs on the cellular level for Alzheimer’s disease?
Extracellular Plaques of Beta amyloid
Intracellular Tangles of hyperphosphorylated Tau proteins
Describe what happens in abnormal function of Amyloid precursor protein (APP)
Cleavage of APP creates Amyloid beta peptides that form oligomer aggregates
Mutations in what are associated with early onset Alzheimer’s disease?
Presenilin 1 and 2
Affect activity of gamma-secretase
Describe function of ApoE
Cholesterol transport
Clears amyloid beta
What are the 3 alleles of ApoE?
E2, E3 and E4
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
What is the function of Tau protein?
Binds and stabilises microtubules (in neurons)
Describe Prion Diseases
Transmissible spongiform encephalopathy
What are 3 examples of Prion diseases?
Creutzfeld-Jakob disease
Fatal familial insomnia
Kuru
Describe a Prion
Proteinaceous
Infectious
Carries no genetic material
What forms of therapy can be used for Prions?
Stabilising PrP^C conformation
Clearance of PrP^SC
Vaccination against PrP^SC
What are the 2 muscles responsible for accommodation of pupil?
Dilator pupillae
Sphincter pupillae
With asymmetrical pupils, what may cause larger pupils?
3rd nerve palsy
Sphincter damage
Drugs
With asymmetrical pupils, what may cause smaller pupils?
Horner’s syndrome
Uveitis
Drugs
What is the main sign of Glaucoma, and what is it often associated with?
Cupping
Raised intraocular pressure
What layers of the Lat. Geniculate nuc. receive ipsilateral and contralateral?
Ips. - 2, 3, 5
Cont. - 1, 4, 6
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
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
What is the function of the Occipital lobe?
Relay station
Retinotopic map
Neural tuning responds to:
1. colour
2. spatial frequency
3. orientation
What is the most common cause of Amblyopia?
Uncorrected refractive error in ONE eye
What are some treatments for Amyblyopia?
Patching
Glasses
Corrected squint
What eye issues may lead to a retinal lesion?
AMD
Diabetic eye disease
Retinal detachment
What issues may lead to a Chiasmal lesion?
Pituitary tumour
Craniopharyngioma
What issues may lead to post Chiasmal lesions?
Stroke
Space occupying lesions
(Tumours + Bleeds)
What are the two separate functional streams of visual information?
‘What’
and
‘Where’
Give some examples of common Motor neuron diseases
-Amyotrophic Lateral Sclerosis (ALS)
-Progressive Bulbar Atrophy
-Primary Lateral Sclerosis
-Spinal Muscular Atrophy
What makes up a Motor Unit?
Motor neurons
and
group of innervated muscle fibres
What are the 4 types of Motor Unit Disorders?
- Motor Neuron Disease
- Peripheral Neuropathies
- Diseases of the NMJ
- Primary Muscle Disease
How would the origins of 90% of ALS cases be described?
Sporadic
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
What are some signs of ALS?
Focal weakness and clumsiness
Painful fasciculations / cramps
UMN and LMN signs
Dysarthria, Dysphasia or respiratory issues
What often degenerates in ALS?
Corticospinal tracts
(B - mild C - severe)
Describe the pathology of Alzheimer’s disease
65+ y/o
Neuronal cell death in Entorhinal cortex and Hippocampus
Cortical atrophy
Amyloid plaques + hyperphosphorylated tau
What percentage of Alzheimer’s disease are Sporadic or Familiar
Sporadic - 90%
Familiar - 10%
What is Braak staging?
Pathological, post-mortem assessment of tau neurofibrillary and beta-amyloid progression based on brain anatomical distribution
Describe the pathology of Parkinson’s disease
Neuronal loss in substantia nigra
degeneration of nigrostriatal tract
Profound loss of dopamine in basal nuc.
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)
What are the 3 types of CJD (Creutzfeldt-Jakob disease)?
Familial
Sporadic
Acquired
What are some symptoms of CJD?
Rapidly developing dementia
Difficulty walking
Muscle stiffness and fatigue
Speech problems
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
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
Give some examples of Inherited muscle diseases
- Dystrophies
- Congenital myopathies
- Metabolic
- Myotonic
Give some examples of acquired muscle diseases
Inflammatory
Toxic (alcohol)
Metabolic
Disuse atrophy
Describe Duchenne Muscular Dystrophy
X-linked recessive trait that affect male in early childhood
Mutation in DMD gene
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
Glioma Grading
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
