Seizures and LOC Flashcards
NMDA receptor responds to
Glutamate
Glycine
What must be dislodged from NMDA receptor before the channel can open?
Magnesium
Open NMDA receptor
Influx of sodium and calcium
Efflux of potassium
Activation of NMDA receptor leads to
ion changes the facilitate depolarization
AMPA receptor activated by
binding of neurotransmitter
Glutamate is the example in lecture
Activation of AMPA receptor leads to
influx of sodium
efflux of potassium
influx of calcium is variable –
Kainate receptor activated by
neurotransmitters
glutamate is example in lecture
Activation of Kainate receptor leads to
influx of sodium
efflux of potassium
variable influx of calcium
Post synaptic kainate receptor
allows for excitation
pre synaptic kainate receptor
inhibition
inhibits the release of GABA
is GABA-A receptor a post synaptic or presynaptic receptor
post synaptic receptor
Binding of GABA-A leads to
influx of chloride –> IPSP of -70 mV (hyper polarization)
What type of receptor is GABA-B
metabotropic receptor that affects ion channels
leads to hyperpolarization
Presynaptic GABA-B receptor
decreased calcium influx
Postsynaptic GABA-B receptor
increased potassium efflux
Voltage gated ion channels —- how it works
stimulus –> conformation changes of Na+ channels –> influx of sodium (fast response) –> depolarization –> delayed potassium opening –> potassium efflux –> hyper polarization
Most pharmacotherapy for seizure is directed at
regulating the voltage gated ion channels
What medications target the GABA receptors
Benzodiazepines
Bind to GABA A receptor to open chloride channels
Hypocalcemia and seizure
low serum calcium level increases our membrane resting potential meaning that it doesn’t require as much for that action potential to be reached so we need little change for that action potential to happen –> so we are in a hyper excitable state
Can also lead to decreased inhibition of sodium channels which allows more sodium to come in which allows more depolarization
Normally, K+/Ca2+ channels are activated by intracellular Ca2+ so if low Ca2+, then channels won’t open which prevents K+ from leaving so the cell won’t be able to hyper polarize
Hypomagnesemia and seizures
No Mg2+ blocking NMDA receptor —> ability for Ca2+ influx –> more depolarization
Hyponatremia and seizures
if intracellular fluid of sodium is greater than extra cellular fluid then we know that water will follow and will cause edema which lowers the threshold
Status epilepticus definition
greater than or equal to five minutes of continuous seizures
OR
greater than or equal to 2 discrete seizures between which there is incomplete recovery of consciousness in a 30 min window
Early in status epilepticus
cerebral auto regulation is turn off which is the ability of the brain to maintain the same blood flow pressure in a wide range of blood pressures
leads to increased systemic blood pressure –> increased cerebral blood flow
Allows for oxygen and glucose delivery to neuronal cells
Able to sustain aerobic metabolism
During status epilepticus
increased ion pumping –> increased metabolic demand –> increased ventilation and oxygen delivery –> switch to anaerobic respiration –> lactic acid build up
Late status epilepticus
lactic acid build up –> peripheral vasodilation
decreased systemic blood pressure –> decreased cerebral blood flow
decreased oxygen and glucose delivery to neuronal cells
cardiac issues in status epilepticus
high output heart failure
autonomic nervous sytem activation (PNS and SNS) –> incongruent signals –> ventricular arrhythmia
skeletal muscle contractions in status epilepticus
increased metabolism –> increased lactic acid production –> acidic environment for neuronal cells
muscle breakdown –> K+ release –> hyperkalemia –> increased extracellular K+ –> inability for K+ to efflux from neuronal cells –> unable to hyper polarize
muscle breakdown –> rhabdomyolysis –> damage to kidneys –> renal tubular necrosis
hyper pyrexia (high fever) due to excessive muscle contractions
Pulmonary issues in status epilepticus
diaphragm contraction –> hypoventilation –> decreased oxygen availability –> anaerobic metabolism –> increased lactic acid
diaphragm contraction –> hypoventilation –> CO2 excess –> respiratory acidosis
increased pulmonary pressure –> fluid leak from vessels –> pulmonary edema
aspiration
EARLY autonomic nervous system and glucose
increased insulin (brings down blood sugar) and increased glucagon (increases blood sugar)
glycogenesis in liver –> release of glucose stores
net effect = available glucose to use for energy
LATE autonomic nervous system and glucose
insulin secretion > available glucose stores –> hypoglycemia (bc insulin lowers blood glucose)
Parasympathetic activation in status epilepticus
detrusor muscle contraction –> urination
defecation reflex activation –> defecation
increased secretions including ion bronchial tree
lactic acid in status epilepticus
all of energy usage, muscle contractions, increase lactic acid –> vasodilation –> further decreased cerebral blood flow
decreased pH including in brain –> neuronal cell death
cellular level in the brain for status epilepticus
decreased ATP –> Na+/Ca2+ pump failure –> increased intracellular Ca2+ –> Ca2+ mediated cell damage
free radical release –> neuronal cell death
mitochondria dysfunction –> apoptotic factors released –> neuronal cell damage
Overall status epilepticus
increased muscle activity leads to decreased oxygen and glucose supple
increased energy utilization by neurons and brain leads to decreased oxygen and glucose supply to the brain further damaging neurons
anaerobic respiration causes lactic acid build up and decreased pH –> damaging neurons
widespread organ dysfunction
also note that lack of oxygen and glucose causes us to switch to anaerobic metabolism
Post-stroke seizure has
high morbidity and mortality
Changes in ions related to ischemia, excessive glutamate, and alteration in penumbra tissue lead to
lowering the threshold and increased excitability
what stroke has higher risk of seizure
multi-infarct stroke
for post stroke seizures, morbidity and mortality increased as
time of onset from initial stroke decreases
when are patients more likely to develop epilepsy after stroke
patients who develop seizure 2 weeks post stroke
may be related to glial scarring
Where is reticular activating system located
brainstem
reticular activating system function
maintains consciousness, alertness, and arousal
functions in sleep/wake
filters sensory info
efferent connections to the autonomic NS –> helps control breathing and heart rate
provides inhibitory influence from external stimuli by reducing sensory activity during sleep
Glasgow Coma Scale is composed of three parameters
best eye response, best verbal response, best motor response
Best eye response (4)
4 - eyes open spontaneously
3 - eye opening to verbal command
2 - eye opening to pain
1 - no eye opening
Best verbal response (5)
5 - oriented
4 - confused
3 - inappropriate words
2 - incomprehensible sounds
1 - no verbal response
Best motor response (6)
6 - obeys commands
5 - localizing pain
4 - withdrawal from pain
3 - flexion to pain (decorticate response)
2 - extension to pain (decerebrate response)
1 - no response
GCS 13 or higher
mild brain injury
GCS 9-12
moderate injury
GCS 8 or less
severe brain injury
Decorticate posturing
lesion above red nuclei = above midbrain
forearms flexed, LE’s extended
Decerebrate posturing
lesion below red nuclei = below midbrain
UE’s extended, pronated, hands flexed, LE’s extended
implies more complete disconnect between higher centers and brainstem
more severe, extensive brainstem injury
worse prognosis
Medial longitudinal fasciculus (MLF)
longitudinal fiber bundle –> runs through medullar, pons, midbrain
connects six ocular motor nuclei (3 pairs) (III, IV, VI), vestibular nuclei, upper cervical nuclei
Yokes eye movements; conjugate gaze
Oculocephalic reflex first most important
make sure no cervical injury
Oculocephalic reflex: how to do it
hold eyelids open and move head from side to side
Oculocephalic reflex if brainstem intact
eyes will move in opposite direction of head rotation
dolls eyes response = reflex is present
Oculocephalic reflex is brainstem is injured
eyes are fixed in mid position and will move with head
more severe injury = worse prognosis
Oculocephalic reflex is patient is awake and non-injured
able to “track” or overcome reflex
Oculovestibular testing fast component
nystagmus is directed away from ear stimulated
Oculovestibular testing slow component
eye movement toward cold
Normal response for oculovestibular testing
both components are present
both are in appropriate directions for cold stimulus
Oculovestibular testing response in unconscious patient, brainstem intact
slow response is present toward cold, fast response absent
both eyes respond
Oculovestibular testing response in unconscious patient, lesion of brainstem
both components are absent
eyes remain in fixed position
