Physiology Flashcards
a _____ supplies all the fibres of one motor unit
single alpha motor neuron
muscles that have fine movements have more/fewer fibres per motor unit
roughly = ___ fibres
fewer
10
muscles that are for power have __fibres per motor unit
100-1000s
organisation of muscle:
sarcomere>____>muscle fibre> ____>whole muscle
myofibril
motor unit
skeletal muscle:
___ initiation and propagation involves ___+neuromuscular junction with ____
excitation contraction coupling by ___ entirely from ___
neurogenic
motor units
with Nitrogen Oxide gap junctions
Ca2+ entirely from sarcoplasmic reticulum
gradation of contraction in skeletal muscle is due to ___+___
motor unit recruitment and summation of contractions
in skeletal muscle Ca2+ is released from ___ of ____ when surface AP spreads down ____ => ______
lateral sacs of sarcoplasmic reticulum
T/transverse tubules
excitation-contraction coupling
in skeletal muscle:
Ca2+ binds to ___ which causes ___ to be pulled away from actin binding site so it can bind to myosin
troponin
tropomyosin
Z line to next Z line =
sacromere
skeletal muscle:
ATP in contraction is for ___
in relaxation it ___
contraction = power cross bridges relaxation = release cross bridge and pump Ca2+ into sarcoplasmic reticulum
____ muscle unit recruitment during ___ contractions help prevent skeletal muscle fatigue
asynchronous
submaximal
gradation of tension in skeletal muscle fibres depends on __+__
number of muscle fibres contracting
tension developed by each muscle fibre
tension developed by one skeletal muscle fibre depends on … (4)
thickness of fibre
length of fibre
freq of stimulation
summation of contractions
The AP in skeletal muscle is __+___ meaning it is possible to summate twitches to bring about __ contraction through ___ stimulation of fibres
shorter than resulting twitch + no refractory period
stronger
repetitive fast
if a skeletal muscle is constantly stimulated before it can relax = ___ = ____ contraction
tetanu
maximal sustained contraction
optimum length of skeletal muscle =
at this length ___ can be acheived
resting length of the muscle
maximal tetanic contraction
2 types of skeletal muscle contraction
isotonic
isometric
isotonic contraction in skeletal muscle =
used for:
tension constant as length changes
body movement + moving objects
isometric contraction in skeletal muscle =
used for:
tension develops at constant muscle length
support objects in fixed position + maintain body posture
velocity of skeletal muscle shortening ____ as load increases
decreases
3 types of skeletal muscle fibre
most motor units contain more than one kind
slow oxidative type 1/slow twitch
fast oxidative type IIa / intermediate twitch
fast glycolytic type IIx / fast twitch
Metabolic pathways that supply ATP in skeletal muscle fibre = (3)
transfer of high E phosphate from creatinine phosphate to ATP - immediate ATP source
oxidative phosphorylation (main aerobic source)
glycolysis (main anaerobic source)
main differences between the 3 types of skeletal muscle fibres
enzymatic pathways for ATP synthesis
resistance to fatigue
activity of myosin ATPase
activity of myosin ATPase determines ______ in skeletal muscle fibres
the speed of energy availability for cross bridge formation ie speed of contraction
resistance to fatigue in skeletal muscle fibres is increased if ____
they have a greater capacity for ATP synthesis
slow oxidative type 1 (slow twitch) fibres are for ___
prolonged low-work aerobic activity eg. walking/posture
fast-oxidative type IIa (intermediate twitch) fibres have ___+__ metabolism for ___
aerobic and anaerobic
prolonged moderate work eg. jogging
fast glycolytic type IIx (fast-twitch) fibres have __ metabolism for ___
anaerobic
short term high intensity activity eg. jumping
myosin ATPase activity in the 3 types of skeletal muscle fibres =
slow = low
intermediate and fast = high
speed of contraction in the 3 types of skeletal muscle fibres =
slow = slow
int + fast = fast
resistance to fatigue in the 3 types of skeletal muscle fibres =
slow = high int = int fast = low
oxidative phosphorylation capacity in the 3 types of skeletal muscle fibres =
slow = high int = high fast = low
enzymes for anaerobic glycolysis in the 3 types of skeletal muscle fibres =
slow = low
int =int
fast = high
number of mitochondria and capillaries in the 3 types of skeletal muscle fibres =
slow = many int = many fast = few
myoglobin content in the 3 types of skeletal muscle fibres =
slow = high int = high fast = low
color of fibre in the 3 types of skeletal muscle fibres =
slow + int = red
fast = white
glycogen content in the 3 types of skeletal muscle fibres =
slow = low int = int fast = high
simplest form of coordinated movement
a stereotyped response to specific stimulus
reflex
simplest monosynaptic spinal reflex =
describe it
stretch reflex
-ve feedback to resist stretch and maintain optimum skeletal muscle length
in stretch reflex:
___ stretched causing increased __ in ___ > synapse at ___ > __
coordinated by simultaneous __
muscle spindle firing in afferent neurons alpha motor neurons muscle simultaneous relaxation of antagonistic muscle
in knee reflex:
spinal segment =
peripheral nerve =
L3 +4
femoral
in ankle reflex:
spinal segment =
peripheral nerve =
S1 +2
tibial
in biceps reflex:
spinal segment =
peripheral nerve =
C5+6
musculocutaneous
in brachioradialis reflex:
spinal segment =
peripheral nerve =
C5+6
radial
in triceps reflex:
spinal segment =
peripheral nerve =
C6+7
radial
sensory receptors for stretch reflex
muscle spindle
muscle spindle = ___ collection
specialised muscle fibre
muscle spindles are made up of __ fibres
normal fibres in skeletal muscle =
intrafusal
normal = extrafusal
muscle spindles are found in ___ and parallel to __
muscle belly
extrafusal fibres
sensory nerve endings in muscle spindles are know as
annulospiral fibres
discharge from ___ in muscle spindles ___ as muscle is stretched
annulospiral fibres increases
efferent supply to muscle spindles =
adjust level of __ in spindles so ___ when muscle shortens during contraction
gamma motor neurons
tension
maintain sensitivity
the contraction of intrafusal fibres does/doesn’t contribute to the overall strength of muscle contraction
doesn’t
in congenital myopathies: ___ changes => decreased ___
microscopic
contractile ability
muscular dystrophy = ____ of contractile elements
chronic degeneration
myotonia is an example of an abnormality in ___
muscle membrane ion channels
4 broad types of acquired myopathies
inflammatory
toxic
endocrine
non-inflam
delayed relaxation after voluntary contraction =
myotonia
EMG aka
detects ___
differentiates ___ from ___
usually do __ at same time as this test is not pathognomic
electromyography
presence of muscle activity - freq and amplitude of APs
primary muscle disease from weakness due to neurological disease
nerve conduction study
5 useful tests in neuromuscular disease
muscle biopsy EMG inflam markers muscle enzymes nerve conduction studies
motor neuron branches end in a ___ at NMJ
terminal bouton
the cell body of motor neurons is in ____
the ventral horn of the spinal cord (or brain stem)
motor neurones release ___ at NMJ which activates ___ a ___ of glycoprotein subunits ((α1)2β1δε) - in embryonic muscle ε is replaced by _
ACh
Nicotinic ACh post-synaptic receptors
pentamer
γ
Nicotinic ACh post-synaptic receptors in muscles are closed unless ____ and then they are ___ selective
2ACh bind
cation selective
Nicotinic ACh post-synaptic receptors in muscles are roughly equally permeable to __+__
direction of movement?
which one has a larger driving force and causes depolarisation (___)
Na+ in to muscle cell + K+ out
Na+ > driving force => end plate potential / epp
each ACh vesicle contains one ___ of ACh
the electrical response to one vesicle’s ACh =>___
quantum
mepp (miniature end plate potential)
End plate in muscles have \_\_\_ adjacent to Nicotinic ACh post-synaptic receptors function = \_\_\_
voltage-activated Na+ channel
AP propagates from the endplate over the length of the muscle fibre without deteriorating
bouton synapse at the ____ of skeletal muscle fibre
endplate region
APs propagate over the surface membrane (____) of skeletal muscle fibre and enters ____
this causes _____ from ___
sarcolemma
transverse (T) tubules
Ca2+ from the sarcoplasmic reticulum
termination of AP in muscle cells:
___ hydrolyses __>choline(__) + acetate (___)
AChE - ACh
taken up into transporter
diffuses from cleft
terminal bouton is surrounded by ___
Schwann cell
ACh vesicles at NMJ await release at “___”
active zones
choline is recycled in the pre synaptic bouton:
choline + ___ > (enzyme) > ACh
acetyl Co-A
CAT
the location of nicotinic ACh receptors in muscle cells
end plate
neuromyotonia aka __/_
s+s
usually acquired = ___ against ____ in motor neurone => ____
NMT/ Isaac’s syndrome
cramps, stiffness, myotonia (slow relaxation), fasciculations (twitches)
AI Ig - voltage activated K+ channels - hyperexcitability
Rx for neuromyotonia/Isaac’s syndrome
anticonvulsants - eg carbamazepine, phenytoin
they block Na+ channels and may also increase inhibitory GABA
v rare and ass with small cell lung ca => muscle weakness
Lambert-Eaton Myasthenic Syndrome (LEMS)
AI process in Lambert-Eaton Myasthenic Syndrome (LEMS)
Ig against Ca2+ channels in neurone terminal => decreased Ca2+ entry and ACh release
Rx of Lambert-Eaton Myasthenic Syndrome (LEMS)
anticholestinesterases (pyridostigmine)
K+ channel blockers (3,4 - diaminopyridine)
___ muscle weakness can transiently improve on exertion, ____ is progressive muscle weakness during activity
Lambert-Eaton Myasthenic Syndrome (LEMS) Myasthenia Gravis (MG)
AI mechanism behind Myasthenia Gravis
Ig against nicotinic ACh receptors => decreased epp amplitude
Rx for myasthenia gravis =
antichloniesterases - edrophonium (to diagnose), pyridostigmine (long term)
IS eg azathioprine
very potent toxin that irreversibly inhibits ACh release at NMJ
no Rx, just time, v high mortality rate
Botulinum Toxin
low dose botulinum haemoglutin complex IM is used for ___ eg __+__
dystonias - strabismus/blepharospasm
To induce reversible paralysis in Sx = ___ compounds eg __/__
they interfere with ____ as antagonise ____ and decrease ___
curare-like vecuronium atracurium post-synaptic ACh nicotinic ACh receptors epp amplitude
synarthosis =
fibrous joints
amphiarthrosis =
egs (4)
cartilaginous joints
IV discs, pubic symphysis, part of SIJ, costochondra
diarthrosis =
synovial joint
synovial membrane lines ____
it is a __ CT with ___ networks and ___ ; they contain ___ that produce ___
fibrous capsule in synovial joints vascular CT capillary networks lymphatics synovial cells (fibroblasts) => synovial fluid
> 1 pair of articular surfaces in a synovial joint = a ___ joint
compound
most of the stress across a synovial joint is taken up by __+__
tendons and muscles across the joint
joint lubrication at diarthroses = (3)
cartilage interstitial fluid
synovium
synovium-derived lubricin-glycoprotein
synovium is derived from ___(__) a polymer of __
hyaluronic acid (mucin) disaccharides
function of synovial fluid
lubrication
supplies chondrocytes with O2 and nutrients
removes CO2 and waste
high viscosity of synovial fluid is due to ___
viscosity varies with ___ as does elasticity
mucin
joint movement
other constituents of synovial fluid eg. uric acid are derived by ___
dialysis of blood plasma
normally synovial fluid contains a few cells - mainly ___
mononuclear luecocytes
rapid movement at a synovial joint => synovial fluid viscosity ___ and elasticity ____
is defective in ___
viscosity decreases
elasticity increases
diseased joint eg OA
colour of synovial fluid in trauma
red
colour of normal synovial fluid and in an inflammatory joint
norm = colourless inflam = straw yellow
clarity of synovial fluid normally, in inflammation and in septic joint
norm = transparent inflam = translucent septic = opaque
WBC count (/mm^3) in synovial fluid normally, in inflammation and in septic joint
norm = <200 inflam = 2000-75000 septic = >100,000
PMN leucocytes (/mm^3) in synovial fluid normally, in inflammation and in septic joint
norm = <25 inflam = >50 septic = >75
zones in articular cartilage superficial to deep =
differ in their ___ and ___
superficial > middle > deep(all chondrocytes) > calcified zone
organisation of collagen fibres
content of cartilage components
usually articular cartilage is __ cartilage
hyaline
articular cartilage has special ___ : 70% ___, 20% ___, 10% ___
ECM
70 water
20 type II collagen
10 proteoglycans
properties of water in articular cartilage (3)
uneven distribution (80% near art. surface) decreases with age maintains tissue resilience
properties of type 2 collagen in articular cartilage (2)
decreases with age
provides stiffness and strength
proteoglycan in articular cartilage: high concn in \_\_+\_\_ zone composed mainly of \_\_ eg \_\_\_ \_\_ changes with age eg decreased amount of \_\_\_ function =
middle and deep
glycosaminoglycan eg chondroitin sulfate
composition - condroitin decreases
compression for load bearing
degradation of ECM in articular cartilage is by ___ from chondrocytes eg __+__
metalloproteinase proteolytics
collagenase + stromelysin
98% of articular cartilage volume =
maintained degraded, synthesised and organised by __
ECM
chondrocytes
chondrocytes get nutrients and O2 from __
synovial fluid
catabolic factors in articular cartilage matrix turnover (2)
TNFα + IL-1
=> stimulate proteolytic enzymes and inhibit proteoglycan synthesis
anabolic factors in articular cartilage matrix turnover (2)
TGF-β and IGF-1
=>stimulate proteoglycan synthesis and counteract IL-1 effects
markers of articular cartilage degradation = increased __+___
____ in synovial fluid
serum and synovial keratin sulfate (^ in age and OA)
type 2 collagen (RA + OA)
pain definition =
an unpleasant sensory and emotional experience associated with actual tissue damage or described in terms of such damage
nociceptive pain is ___ (early warning sign) and ___ (only to intense stimuli)
adaptive
high threshold
___ overrides other nervous system activities eg. => withdrawal reflex
nociceptive pain
nociceptors = specific _____ activated by ___ stimuli.
are ___ order and relay to ___ at __ synapse
stimuli =__/__/__
peripheral primary sensory afferent neurones
intense noxious
1st order - 2nd order - CNS
temp / mechanical force / chemical irritants
inflammatory pain is __(early warning system) +__
caused by activation of ___
=> ___+___
adaptive + protective
immune system to injury/infection
pain hypersensitivity and allodynia
inflammatory pain discourages __+___ so aids healing
physical contact and movement
maladaptive pain = ___ pain
due to _____
2 types =
=> __/___
pathological abnormal nervous system functioning neuropathic (neural lesion +/- symptoms) dysfunctional (no neural lesion but +ve symptoms) spontaneous pain/pain hypersensitivity
Congenital insensitivity to pain (CIP) is caused by which mutation? that encodes __ which is highly expressed in nociceptive neurones
loss of function (missense/inframe deletions) in SCN9A
voltage gated activated Na+ channel (NaV1.7)
nociceptors are comprised of __+__ fibres
Aδ + C
Aδ fibres = __/___ nociceptors - ___ myelinated
mediate __/__ pain
mechanical / thermal
thinly
1st / fast
C fibres are ___ (respond to all noxious stimuli) and ___ so mediate __/__ pain
polymodal
unmyelinated - 2nd/slow
thermal stimuli to C fibres activate ____ esp. ___ - it is greatly sensitised in inflammation and so becomes active at ___
Transient receptor potential family (TRP)
esp. TRPV1
body temperature
in chemical stimulation of C fibres:
H+ activates ___
Atp activates ___
bradykinin activates ____
ASIC (acid sensing ion channels)
P2X+ P2Y receptors
B2 receptors
possible receptor to mechanical stimuli in C fibres
Piezo2
all stimulation of c fibre receptors cause __/__ influx > graded ___ > ___ activated > aP to CNS
Na+ Ca2+
depolarisation
voltage gated Na+ channels
amplitude of depolarising receptor/generator potential in C fibres is __ and proportional to ___
graded
stimulus intensity
local current flow (___) in c fibres trigger all/none APs at frequency proportional to ___
Hermann currents
receptor potential
axon of 1st order neurone nociceptor synapses in _____
its soma is in ____/____
axon of 2nd order neurone > ___+___ > pain
ducussation via ____ occurs at all levels of the spinal cord
dorsal/posterior horn of spinal cord
dorsal root ganglion (DRG) / trigeminal ganglion (TG)
spinothalmic + spinoreticulothalmic tracts
ventral white commisure
subset of C fibres = ___ polymodal nociceptors
afferent - release __+__ to CNS at dorsal horn synapse
efferent - releases ____ and contributes to ___
peptidergic
glutamate + peptides (substance P and neurokinin A)
pro-inflam mediators (eg calcitonin gene related peptide (CGRP) and substance P)
neurogenic inflam
neurogenic inflam:
___(__+__) from peptidergic nociceptor free nerve endings are released due to __/____
peptides (substance P and CGRP -calcitonin gene related peptide)
inflammatory mediators/tissue damage
role of substance P released in neurogenic inflammation (3)
vasodilation and extravasation of plasma proteins (promotes formation of bradykinin and PGs)
histamine released from mast cells
sensitises surrounding nociceptors
the role of CGRP released in neurogenic inflammation
vasodilation
CGRP and substance P cause effects in neurogenic inflammation that ultimately lead to ___
primary and secondary hyeralgesia and allodynia
in pain: primary afferent to 2nd order neurone in dorsal horn transmission =
AP > ___ influx > __ released from afferent
> __ epsp and neuronal excitation by activating ___ and some NMDA receptor involvement > depolarisation of 2nd neurone and ___ open > AP
Ca2+ glutamate fast postsynaptic AMPA receptors Na+ channels
in pain: primary afferent to 2nd order neurone in dorsal horn transmission:
__+___ are also involved esp in high freq stimulation = __+__ epsp that facilitates ___ activation by relieving voltage dependent block by __
substance P CGRP slow and prolonged NMDA receptor Mg2+
for pain: primary afferent cell bodies (except in trigeminal system) are located in the ___ - axon terminates centrally in the ___ in various ___
DRG
dorsal horn
lamina Rexed
nociceptive C and Aδ mostly terminate in __+__ also + __ for Aδ
laminae I+II
V for Aδ too
nociceptive specific cells synapse only with __+_
C and Aδ fibres
cells that receive input from Aβ fibres are ___
proprioceptive
wide dynamic range (WDR) neurones receive input from ++_
Aβ, C and Aδ fibres
in nociceptive tract for 2nd order neurones:
in spinothalmic tract:
projecting neurones from ___ (fast fibre ___ pain) terminate in ___
projecting neurones from ___ (WDR) terminate in __+__
pain perception (site and intensity) need ___ firing from both pathways
lamina I - Aδ - posterior nucleus of thalamus
lamina V - posterior and ventroposterior nucleus of thalamus
simultaneous
in nociceptive tract for 2nd order neurones:
in spinoreticular tract: mainly transmits ___ __ fibre pain
makes extensive connections with ___ in ___ eg periaquesductal grey (PAG) + _____
involved in ___ responses to pain, arousal, emotion and fear of pain
slow C
reticular nuclei in brainstem
parabrachial nucleus (PBN)
autonomic
