Pathologies Flashcards
(94 cards)
1
Q
Epilepsy
A
A condition in which patients have recurrent, unprovoked epileptic seizures
2
Q
Epileptic seizure
A
An abnormal and excessive electrical discharge from neurons in the cerebral cortex
May occur when there is an imbalance between excitatory and inhibitory neurons
3
Q
Focal seizure
A
Involves the neurons in one part of the brain
Also called partial
4
Q
Generalised seizure
A
Involves all neurons of the brain
Both hemispheres are involved
5
Q
Focal aware seizure
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Consciousness preserved
Also called simple partial seizure
6
Q
Focal impaired awareness seizure
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Involves deep structures of the brain and brainstem where consciousness is not preferred
Also called complex partial seizure
7
Q
NMDA receptors
A
Activated by NMDA
When occupied, Na+, K+ and Ca+2 channels open
When hyperpolarised, Mg+2 blocks the channel causing partial depolarisation. Mg+2 expelled, positive feedback loop occurs.
8
Q
Non-NMDA receptors
A
Activated by AMPA and kainic acid
Ion channel permeable to Na+ and K+ but impermeable to Ca+2
Rapidly activated and inactivated
9
Q
Tonic
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Stiffness
10
Q
Clonic
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Rhythmic jerking
11
Q
Myoclonic
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Repeated but isolated jerks
12
Q
Absence
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Blankness
13
Q
Atypical absence
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Prolonged blankness
14
Q
Excitatory transmission in epilepsy
A
Depolarisation of presynaptic terminal results in entry of Ca+2
Fusion of vesicles with presynaptic membrane causing exocytosis of contents into synaptic cleft
Non-NMDA channels open quickly and produce partial depolarisation resulting in Mg+2 expulsion from NMDA channels
Further Ca+2 entry and further depolarisation
15
Q
Inhibitory transmission in epilepsy
A
GABA receptors linked to ion channels that bind two molecules of GABA
Cl- channels open which hyperpolarises the neuron
16
Q
3 drugs that induce seizures by blocking GABA receptors
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Penicillin
Picrotoxin
Bicuculline
17
Q
2 things that induce seizures by activating glutamate receptors
A
Kainate and domoic acid (shellfish)
18
Q
How can low magnesium induce seizures?
A
By unblocking NMDA receptors, causing NMDA channels to open and Ca+2 to rush in and depolarise the cell membrane
19
Q
How does strychnine induce seizures?
A
By blocking glycine receptors
20
Q
How does 4-aminopyridine induce seizures?
A
By blocking potassium currents
This is an MS drug which helps to treat spasticity
21
Q
Examples of Na+ channel blockers to treat epilepsy
A
Phenytoin and carbamezapine
22
Q
How do Na+ channel blockers treat epilepsy?
A
They act on voltage sensitive Na+ channels of excitatory neurons and stabilise Na+ currents in inactive form, preventing sustained repetitive firing from extended depolarisation
23
Q
3 drugs that block glutamate transmission
A
Topirimate
Felbamate
Lamotrigine
24
Q
3 drugs that enhance GABAergic transmision
A
Benzodiazepines
Phenobarbitone
Vigabatrin
25
3 possible mechanisms for the induction of epilepsy
1) Anatomic rearrangement of local circuits. Neuronal death is thought to cause sprouting of unlesioned axons to fill in dendritic regions forming new circuits causing seizures.
2) Frequency dependent changes in synaptic efficacy. Excitatory synapses potentiated when they fire repetitively whereas inhibitory synapses tend to decrease in efficacy when fired repetitively.
3) Changes in local receptors. NMDA receptors may change after neuronal injury, meaning epilepsy could be a vicious cycle.
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Atonic
Sudden loss of muscle tone
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Idiopathic epilepsy
Brain is normal apart from a tendency to seizure
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Symptomatic epilepsy
Occurs when epilepsy is secondary to a known neurological disorder
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Cryptogenic epilepsy
Occurs when there are other features but the underlying pathology has not been identified
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4 types of paralysis
Monoplegia
Hemiplegia
Paraplegia
Quadriplegia
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Injuries that tend to cause focal, acute lesions
Trauma, vascular disease
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Injuries that tend to cause diffuse, acute lesions
Toxins, infection
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Injuries that tend to cause focal, chronic lesions
Brain tumour
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Injuries that tend to cause diffuse, chronic lesions
Neurodegeneration
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Locations of motorneurons
Motor nuclei in the spinal cord – anterior horn cells
| Motor nuclei in the brainstem – III–XII
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Alpha motorneurons
Innervate extrafusal muscle fibres
| Directly responsible for the generation of force by muscles
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Gamma motorneurons
Innervate intrafusal muscle fibres
| Located near alpha motorneurons and control excitability of stretch receptors in muscle spindles
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Myopathy
Disease of muscles
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Neuropathy
Disease of motorneurons
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Muscular dystrophy
A group of inherited disorders characterised by deficits in muscle proteins and progressive muscle weakness and wasting
Duchenne's is overall most common, myotonic is the most common adult muscular dystrophy
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Myotonia
Failure of muscles to relax immediately after contraction
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Myotonic muscular dystrophy
Characterised by myotonia, hypotonia, stiffness, muscle weakness and muscle wasting
Inherited in a dominant fashion due to triple CTG repeats
Onset around 20–30
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Myasthenia gravis
Autoimmune disease characterised by fewer ACh binding sites, therefore a smaller amplitude of end-plate potentials and decreased synaptic transmission
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Two ways of testing for myasthenia gravis
1) Injecting edrophonium, an AChE blocker allowing ACh to not degrade meaning symptoms abate. This only lasts for a short period of time but can result in intense side effects so patients often pretreated with atropine, an anticholinergic.
2) Anti-AChR antibody detection blood test – only 85% of patients express these antibodies
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Botulism
Disease caused by botulinum toxin from Clostridium botulinum. Toxins impair ACh release at all peripheral cholinergic synapses, affecting striated and smooth muscle equally.
Toxin binds nerve terminal and is endocytosed, causing proteolysis of membrane proteins involved in neurotransmitter release causing eventual muscle paralysis
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Wallerian degeneration
Degeneration of the distal axon when damaged or cut. Loss of synaptic transmission with 24 hours, then degeneration after a few days.
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Axotomy
Axon injury causing Wallerian degeneration, chromatolysis (changes in the proximal axon) and eventually axon regeneration and reinnervation of muscles (in the peripheral nervous system – CNS axons don't regenerate)
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Two types of peripheral neuropathy
Diabetic neuropathy
| Guillian–Barre syndrome
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Symptoms of lower motorneuron disease
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Atrophy
Muscle wasting/weakness/paralysis
Depressed or abolished tendon reflexes
No spasticity
No Babinski reflex
Signs of muscle denervation
```
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Signs of muscle denervation
Fasciculations (coarse twitching) and fibrillations (discharge of single muscle fibres)
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3 examples of diseases affecting cell bodies of lower motoneurons
Polio
Syringomyelia
ALS
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Poliomyelitis
Acute viral infection causing focal degeneration of motoneurons and muscles resulting in weakness or paralysis
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Syringomyelia
Formation of large cysts within the central portion of the spinal cord
Damage of pain and temperature fibres followed by the damage of motoneuron cell bodies
Pathogenesis unknown
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ALS
Hardening of the lateral parts of the spinal cord, affecting the motoneurons themselves and the upper motoneurons in the cerebral cortex. This leads to severe weakness of various groups of muscles.
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ALS symptoms
Progressive wasting, weakness and atrophy
Paralysis
Dysphagia
Dysarthria
Impairment of respiration – increases chance of pulmonary infection
Fibrillations and fasciculations
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What areas are not involved in ALS?
Anal and bladder sphincters
| Sensory/intellectual systems
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5 hypotheses of ALS
1) Autoimmune
2) Neurotrophic
3) Oxidative stress
4) Fas-induced cytotoxicity
5) Excitotoxic hypothesis
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Autoimmune hypothesis of ALS evidence
Presence of antibodies against calcium channels in some patients
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Neurotrophic hypothesis of ALS
Reduction in the level of neurotrophic factors which promote motoneuron survival
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Oxidative stress hypothesis of ALS
Damage of motoneurons by free radicals
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Fas-induced cytotoxicity hypothesis of ALS
Increased sensitivity to Fas which increases expression of neuronal NOS
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Excitotoxic hypothesis of ALS
Increased extracellular glutamate and reduced expression of GluR2 subunit of AMPA glutamate receptor
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ALS treatment
Riluzole – glutamate release blocker, can slow disease progress by a few months
Baclophen – GABA-B receptor agonist, reduces spasticity
Symptomatic treatments e.g. control of excessive salivation
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Two types of meninges
Dura, with periosteal and meningeal layers
| Leptomeninges, with pia and arachnoid mater
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Subarachnoid space
Lies between arachnoid and pia mater
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Virchow-Robin spaces
As blood vessels enter or leave the brain or spinal cord, the pia is invaginated into the brain or spinal cord to form a perivascular space
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Epyndema
Single layer of cells lining the ventricles of the brain
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Where is the CSF formed?
By the choroid plexus in the lateral ventricles and a small amount from the interstitial fluid of the brain by bulk flow along perivascular spaces and axon tracts
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How is the CSF formed?
Filtration across the choroidal capillary wall
| Active secretion by the choroidal epithelium
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CSF circulation
Flows from the lateral ventricles into the midline third ventricle through the foramina of Monro
Then from the third ventricle through the cerebral aqueduct to the fourth ventricle
Then leaves the fourth ventricle via the foramen of Magendie and the foramina of Luschka to enter the subarachnoid space
Collects in the subarachnoid cisterns surrounding the brainstem and circulates in the subarachnoid space, then extends into the perivascular spaces
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Yellow CSF
Indicates leaching of haemoglobin breakdown into the CSF (xanthochromia)
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Cloudy CSF
Indicates buildup of white blood cells or protein which is characteristic of infection
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Where should you do a lumbar puncture?
Most often between L3 and L4, but anywhere below L2
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4 key functions of CSF
Homeostasis
Mechanical protection
To counter sudden increase in ICP
Conduit for hormones
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Normal CSF pressure
65–195 mm of CSF or water
| Equivalent to 5–15 mmHg
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2 ways to measure ICP
Lumbar puncture
| Continuous monitoring by intercranial pressure monitoring devices
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4 compensatory mechanisms for ICP
1) Displacement of CSF from intercranial cavity through foramen magnum into spinal subarachnoid space
2) Collapse of cerebral veins to reduce ICP
3) Increase in the absorption of CSF to decrease intercranial CSF volume
4) Distensibility of lumbosacral dura
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Monro-Kellie doctrine
When the volume of one component increases, the volume of another must decrease. If not, the ICP increases.
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3 causes of ICP
1) Increase in volume of the brain by space-occupying lesion
2) Increase in volume of CSF in intracranial cavity
3) Increase in cerebral blood volume
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3 ways that CSF could increase in volume in the intracranial cavity
1) Obstruction of CSF flow
2) Reduced absorption of CSF
3) Overproduction of CSF by a choroid plexus papilloma
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2 ways that cerebral blood flow could be obstructed
1) Obstruction of cerebral venous outflow
| 2) Loss of cerebrovascular autoregulation
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3 types of brain oedema
1) Vasogenic oedema
2) Cellular oedema
3) Interstitial oedema
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Vasogenic oedema
Increased volume of ECF in the brain caused by increased permeability of endothelial cells in the brain to albumin and other molecules normally excluded by the BBB
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Cellular oedema
Intracellular swelling of neurons, glia and endothelial cells caused either by energy depletion and failure of ATP-dependent sodium pumps, allowing water and sodium to accumulate in cells or acute plasma hypo-osmolality
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Interstitial oedema
Increased water and sodium content in periventricular white matter due to transepyndymal absorption of CSF in patients with hydrocephalus
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3 forms of cerebral herniation
1) Midline shift
2) Herniation of medial temporal love through tentorial notch
3) Herniation of inferior cerebellum from posterior fossa into spinal canal
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Cushing's triad
1) Arterial hypertension
2) Slow HR
3) Slow RR
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Systemic factors that affect ICP
1) Arterial blood pressure
2) Venous pressure
3) Intrathoracic pressure
4) Posture
5) PaCO2
6) PaO2
7) Temperature
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3 functions of the BBB
1) Regulation of ion balance in the brain
2) Facilitation of transport of essential substances
3) Barrier against entry of potentially harmful molecules
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How do endothelial cells in the CNS differ from endothelial cells in other parts of the body?
In the brain, they don't have fenestrations and do have tight junctions. They have fewer pinocytotic vesicles and thicker basement membranes. They have astrocytic foot processes close by.
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5 factors that affect transport across the BBB
1) Molecular weight of the molecule
2) Lipid solubility
3) Ionisation
4) Protein binding
5) Specific transport systems
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Disorders of the BBB
Disruption of tight junctions
Proteolysis of basement membranes
Disruption of endothelial cell–glial cell interactions
Altered function of specific transporter mechanisms
New blood vessels forming in brain tumours
Congenital issues
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Effects of brain tumours on the BBB
Abnormal blood vessels can form which can be leaky, allowing interstitial fluid to accumulate and causing oedema
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Effects of meningitis on the BBB
Inflammatory response causes BBB breakdown
