neurophysio
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NeuroPhysiology
Claire R. Berbano. MD
Human Central Nervous System
contains 100 billion neurons
Includes the neurons, the building blocks of the CNS
Main function of the neuron is to integrate and transmit nerve impulses
Glial Cells
comes from the Greek word glia for glue
2 major types:
Microglia scavenger cells like macrophages that removes debris frominfection or injury
Macroglia consists of oligodendrocytes, Schwann cells and astrocytes
Astrocytes
2 subtypes:
Fibrous astrocytes intermediate filaments found primarily in white matter
Protoplasmic astrocytes contains granular cytoplasm found in gray matter
Send processes to capillaries inducing them to form the blood-brain barrier
Axonal Transport
nerve cells have low threshold for excitation wherein the stimulus could
either be electrical, chemical or mechanical
Axosplasmic flow provides transport of proteins and polypeptides to axonal
ending
Orthograde transport = cell body to axon terminals (kinesin and dynein)
Retrograde transport = axon terminals to cell body
Wallerian Degeneration
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Neurotropins
produced by astrocytes
transported to cell body via retrograde transport where they foster the
production of proteins necessary for neuronal growth, development and
survival
the first neurotropin to be recognized is the nerve growth factor (NGF)
others include brain-derived neurotropic factor (BDNF), neurotropin 3 or 4
NeuroPhysiology
Claire R. Berbano M.D.
Nervous System
senses and interprets the environment in an attempt to produce behaviorappropriate to that environment
Components
central nervous system (CNS) brain and SC
peripheral nervous system (PNS)
a.) somatic NS
b.) autonomic NS
Nervous System
Brain is divided into 5 parts:
myelencephalon medulla
metencephalon pons/cerebellum
mesencephalon midbrain
diencephalon thalamus/hypothalamus
telencephalon cerebrum
Cerebrospinal Fluid
supports the brain in the cranium
approximately 600-700 ml is formed each day
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150ml are circulating in the subarachnoid space
not an ultrafiltrate of plasma
higher concentration of Na, Cl and Mg than plasma; while lower concentration
of K, glucose and Ca than plasma
production inhibited by diuretic and corticosteroid
Flow of Cerebrospinal Fluid
choroid plexus
foramina of Magendie/Luschka
3rd ventricle
cerebral aqueduct
4th ventricle
Medial and lateral aperture
subarachnoid space
arachnoid granulations/villi
Blood-Brain Barrier
composed of capillary endothelium and basement membrane of the
vasculature supplying the brain
brain capillaries have tight junctions, no gap junctions
lipid-soluble substances (carbon dioxide, oxygen) cross more easily
not present in pituitary gland, pineal gland, choroid plexus and some parts of
hypothalamus
Blood-Brain Barrier
Functions:
protects the brain from endogenous or exogenous toxins
prevents escape of neurotransmitter from their functional sites in the CNS
inflammation, irradiation and tumors may destroy the blood-brain barrier thus
permitting entry of noxious substances
Cerebral Blood Flow
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about 80ml/100g/min (gray matter) and 20ml/100g/min (white matter)
is autoregulated (BP of 50 to 150 mmHg)
Chronic HPN (>150mm Hg) may disrup the BBB
regional metabolic activity helps determine regional CBF
If PCO2 increases, CBF also increases
If CBF decreases, EEG activity decreases
barbiturates constrict, volatile anesthetic dilates
Intracranial Pressure
contents of the cranium are noncompresible
an increase on one area can be compensated for by a decrease in another
if intracranial volume increases, ICP remains low until the compensatory
mechanisms are overcome, at which time ICP increases fairly rapidly
ICP acutely increase during coughing and Valsalva maneuver
Nerve Fiber Types
Sensory Receptors
Transducers that convert energy in the environment into action potentials in
neurons
Receptors respond by increasing permeability to Na and K producing a
receptor potential
Weber-Fechner law states that the magnitude of the sensation felt is
proprotional to the log of intensity of the stimulus
the generator or receptor potential is the nonpropagated depolarizing
potential in a sense organ after adequate stimulus.
Classification of Sensory Receptors
Sensory Transduction
Sensory Receptors
when a maintained stimulus of constant strength is applied, the frequency of
AP declines with time (adaptation or desenstitization)
Classification of receptors:
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Mechanoceptors touch and pressure
Nociceptors pain, extreme heat or cold
Chemoreceptor change in the chemical composition of the environment (eg.
taste buds, olfactory senses)
Photoreceptors respond to light
a.) phasic receptors
- rapid and react strongly
- ex. Pacinian and Meissners corpuscles
b.) tonic receptors
- adapt slowly and incompletely
- ex. Ruffinis, Merkels disks, muscle spindles and
nociceptors
Pacinian Corpuscle
unmyelinated tip of a sensory nerve surrounded by concentric lamellations
resembling an onion
detects deep pressure and fast vibration
Ruffinis Corpuscle
deep skin receptors with a collagen filled capsule
detects sustained pressure
Meissners Corpuscle
dermal receptors and encode velocity of stimulus application (touch/flutter)
present in non-hairy skin
discriminatory touch and slow vibration
Merkels Disk
disk-like nerve endings that form synaptic connections with small receptive
fields
used for localizations of stimulus
Pain Receptors
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nociceptors, free nerve endings (III,IV)
adapt extremely slowly
bradykinin and histamine released from damaged cells and activate
nociceptors
intensity of pain is related to the extent of tissue damage
report skin pain, visceral pain (poorly localized) and deep somatic pain (ex.
headache)
Pain Receptors
Fast pain
- acute, discretely localized pain (pinprick)
- small myelinated A-delta fibers (III)
- elicits the withdrawal reflex
Slow pain
- diffuse, chronic pain (burning)
- small unmyelinated C fibers
- sweating, nausea, changes in blood pressure and
muscle tone
Pain Receptors
pain impulses = lightly myelinated A and unmyelinated C fibers
cold receptors = dendritic endings of A and C fibers
heat receptors = C fibers
hyperalgesia = exagerrated response to a noxious stimuli
allodynia = sensation of pain in response to an innocous stimuli
Pain Sensations
substance P is the neurotransmitter at the synapses in the dorsal horn from
primary pain afferents
pain perception may be a function of subcortical centers but the cortex is
needed in interpreting the quality of pain
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opiate receptors are seen in substantia gelatinosa and may inhibit substance
P
Pain Sensations
Stress-induced analgesia pain disappears during a period of stress or
concentration on the matter at hand
Referred pain pain referred from a viscus to a somatic structure that shares
the same embryologic dermatome
Projected pain results from actual stimulation of a pain pathway anywhere
along the path causing it to manifest at the periphery of the pain pathway
NeuroPhysiology
Synaptic Transmission
Arrangements:
one to one synapses (NMJ)
- AP in presynaptic (motor nerve) produces an AP in postsynaptic (muscle)
many to one synapses (spinal motoneurons)
- many presynaptic to one postsynaptic cell to depolarize it to threshold.
Neuromuscular Junction
The synapse between axons of a motor neuron and a skeletal muscle fiber
Acetylcholine (Ach)
An acetyl ester of choline
Synthesized in the cytoplasm; catalyze by choline acetyltransferase
Taken up into synaptic vesicles by an active vesicular transport mechanism
Acetylcholinesterase, located in synaptic cleft and weakly associated with
postsynaptic membrane, terminates Ach via hydrolysis to acetate and choline
Choline undergoes active reuptake
Small amount of Ach that diffuses away is degraded by serum and
erythrocyte cholinesterases
Acetylcholine
used by all motor axons, autonomic preganglionic neurons, postganglionic
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parasympathetic, and some cells of motor cortex and basal ganglia
major termination enzymatic degradation
Adrenergic Transmission
similar with cholinergic transmission
the conversion of tyrosine to dopa via tyrosine hydroxylase is the rate-
limiting step and occurs in the cytoplasm
dopamine is converted into NE after vesicular uptake
reuptake is a major mechanism to terminate transmitter activity; second is
via diffusion
COMT is found in smooth muscle, liver and kidney tissues; not found in
adrenergic nerve endings
Formation of Norephineprine
Synapses Between Neurons
synapses are located on the cell body and dendrites
cell body/dendrites = ligand-gated (EPSP, IPSP)
axon/axon-hillock = voltage-gated (low threshold)
if the sum of all the inputs reaches threshold, AP will be generated
Excitatory Postsynaptic Potential (EPSP)
transient depolarization
moves membrane potential closer to threshold
increase conductance to Na and K
Na influx causes depolarization
similar to EPP in NMJ
excitatory neurotransmitters include ACH, NE, Epinephrine, Dopamine,
glutamate and serotonin
Inhibitory Postsynaptic Potential
(IPSP)
transient hyperpolarizations
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moves membrane potential away from threshold
increase Cl conductance
Cl influx causes hyperpolarization
can also be produced by increased K conductance and K efflux
inhibitory neurotransmitters include GABA and glycine
Electrical Synapses
AP is transmitted from one cell to the other by the direct flow of current
can occur in both directions (bidirectional); faster than chemical synapses
(unidirectional)
joined together by gap junctions
Biogenic Amines
NE, epi, dopamine, serotonin and histamine
NE primary NT for postganglionic sympathetic neurons
Epi released by chromaffin cells in adrenal medulla
Serotonin high amounts in brains stem
Histamine hypothalamus
major termination - reuptake
Amino Acid
glycine, GABA, glutamate and aspartate
glycine inhibitory transmitter in spinal interneurons and brainstem
GABA inhibitory NT in CNS
GABA and glycine both generate IPSP via ligand gated Cl channels
Glutamate and aspartate generates EPSP
major termination - reuptake
Nitric Oxide
lipid-soluble; synthesized as needed
not packaged in vesicles nor released via exocytosis
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readily diffuses across cell membranes
an inhibitory transmitter in CNS and ENS
also functions as a cellular signal transduction molecule in neural tissue and
vascular smooth muscle (endothelial-derived relaxing factor)
Agents Affecting Neuromuscular Transmission
Botulinum Toxin
blocks release of Ach from presynaptic terminals
causes total blockade
Curare
competes with Ach for receptors on motor end plate
decreases EPP
maximal dose can produce paralysis of respiratory muscles and death
Agents Affecting Neuromuscular Transmission
Neostigmine
blocks anticholinesterase action
prolongs and enhance action of Ach at muscle end plate
Hemicholinium
blocks reuptake of choline into presynaptic terminals
depletes Ach stores from presynaptic terminal