Flashcards in Physiology Deck (164):
What dictates the number of muscle fibres per motor unit?
Depends on the functions served by the muscle
What does a motor unit encompass?
A single alpha neuron and all the skeletal muscle fibres it innervates
What are the striated muscle types?
Skeletal and cardiac muscle
What nervous system innervates the skeletal muscles?
Somatic- subject to voluntary control
What nervous system innervates cardiac and smooth muscles?
Autonomic-subject to involuntary control
What are the physiological functions of skeletal muscles?
Maintenance of posture, purposeful movement in relation to external environment, respiratory movements, heat production and contribution to whole body metabolism
Do muscles which serve fine movements (e.g.intrinsic hand muscles, extra ocular muscles) have more or fewer fibres per motor unit?
Fewer (~10 per motor unit)
Do muscles in which power is more important than precision, such as thigh muscles, have more or fewer fibres per motor unit?
More (hundreds to thousands per motor unit)
What are the levels of organization in skeletal muscle?
Whole muscle (organ), muscle fibre (one cell), myofibril (Specialised intracellular structure), sarcomere (functional unit)
What dictates the initiation and propagation of contraction of skeletal muscle?
Neurogenic initiation. Motor units present, neuromuscular junction present. No gap junctions
What dictates the initiation and propagation of contraction of cardiac muscle?
Myogenic (pacemaker potential) initiation. No neuromuscular junction. Gap junctions present
What excitation contraction coupling occurs in skeletal muscle?
Ca++ entirely from SR
What excitation contraction coupling occurs in cardiac muscle?
Ca++ from ECF and SR (Ca++ induced Ca++ release)
What accounts for the gradation of contraction of skeletal muscle?
1. Motor unit recruitment. 2. Summation of contraction
What accounts for the gradation of contraction of cardiac muscle?
Depends on extent of heart filling with blood (preload)- Frank-Starling mechanism
What is excitation contraction coupling?
The process whereby the surface action potential results in activation of the contractile mechanism of the muscle fibre
In skeletal fibres when is Ca++ released from the lateral sacs of the SR?
When the surface action potential spreads down the transverse (T)-tubules
What are T-tubules?
Extensions of the surface membrane that dip into the muscle fibre
What is the transmitter at the skeletal neuromuscular junction?
How are skeletal muscles usually attached to the skeleton?
Between what line of a myofibril will you find sarcomeres?
What does the Z-line do?
Connect the thin filaments of 2 adjoining sarcomeres
What are the 4 zones of a sarcomere?
A-band, H-zone, M-line and I-band
Describe the A-band of a sarcomere
Made up of thick filaments along with portions of thin filaments that overlap in both ends of thick filaments
Describe the H-zone of a sarcomere
Lighter area within middle of A-band where thin filaments don’t reach
Describe the M-line of a sarcomere
Extends vertically down middle of A-band within the centre of H-zone
Describe the I-band of a sarcomere
Consists of remaining portion of thin filaments that do not project in A-band
How is muscle tension produced?
Sliding of actin filaments on myocin filaments
What does force generation depend upon in the sliding of actin over myocin?
ATP-dependent interaction between thick and thin filaments
What is ATP required for with regards to muscles?
Both contraction and relaxation
What is Ca++ required for in cross bridge formation?
Switching it on
How does Ca++ switch on cross bridge formation?
Ca2+ binds to troponin. This results in
uncover the cross bridge binding sites on actin
What is ATP needed for during relaxation?
Release cross bridges, and pump Ca++ back into the SR (rigor mortis occurs after death due to this as lack of ATP)
What two primary factors does gradation of skeletal muscle tension depend on?
Number of muscle fibres contracting within the muscle, and tension developed by each contracting muscle fibre
What is motor unit recruitment?
Stimulation of more motor units, to achieve a stronger contraction
What does a synchronous motor unit recruitment during submaximal contractions help prevent?
`What does the tension developed by each contracting muscle fibre in skeletal muscle depend on?
Frequency of stimulation, summation of contractions, length of fibre at onset of contraction, thickness of fibre
What is the duration of action potential in skeletal muscle compared to the duration of the resulting twitch?
How can you summate twitches to bring about a stronger contraction?
Through repetitive fast stimulation of skeletal muscle
What is the maximal sustained contraction that occurs if a muscle fibre is stimulated so rapidly it does not have time to relax between stimuli?
Why can cardiac muscle not be tetanised?
The long refractory period prevents generation of this
How can maximal tetanic contraction be achieved?
When the muscle is at its optimal length prior to onset of contraction
In the body what is approximately a skeletal muscles optimal length?
The resting length
How is skeletal muscle tension transmitted to bone?
As a result of cross bridge cycling via the stretching and tightening of muscle connective tissue and tendon
What is an isotonic contraction used for, and what occurs regarding tension during it?
Body movements and moving objects. Tension remains constant as the muscle length changes
What is an isometric contraction used for, and what occurs regarding tension during it?
Supporting objects in fixed positions and for maintaining body posture. Tension develops at constant length
What happens to the velocity of muscle shortening as the load decreases?
What can impairment of skeletal muscle function be caused by?
Intrinsic disease of muscle, disease of NMJ, disease of lower motor neurons which supplies the muscle, disruption of inputs to motor unit
What are reflex actions?
Stereotyped response to a specific stimulus
What is the simplest monosynaptic spinal reflex?
Is stretch reflex an example of positive or negative feedback?
What does the stretch reflex do to maintain optimal resting length of muscle?
Resists passive change in muscle length
When does the stretch reflex help?
Maintains posture e.g. whilst walking
What is the sensory receptor of the stretch reflex, and what is it activated by?
What does stretching the muscle spindle cause?
Increased firing in the afferent neurons
Where do the afferent neurons involved in the stretch reflex synapse and what with?
In the spinal cord with the alpha motor neurons (efferent limb of stretch reflex) that innervate the stretched muscle
How is the stretch reflex coordinated?
By simultaneous relaxation of antagonist muscle
How can the stretch reflex be elicited?
Tapping the muscle tendon with a rubber hammer
What are muscle spindles known as?
What are ordinary muscle fibres referred to as?
Where are muscle spindles found, and what do they run parallel too?
Within the belly of muscles and run parallel to ordinary muscle fibres
What are the sensory nerve endings of muscle spindles known as?
What happens to the discharge from the muscle spindles sensory endings as the muscle is stretched?
What nerve supply do muscle spindles have?
It's own efferent supply, with gamma motor neurons
What do the gamma-motor neurons that supply muscle spindles do?
Adjust the level of tension in the muscle spindles to maintain their sensitivity when the muscle shorten during muscle contraction
What are the main differences between different types of skeletal muscle fibres?
Enzymatic pathways for ATP synthesis, resistance to fatigue, activity of myosin ATPase
What does an individual motor unit typically contain with regards to muscle fibre?
One type only
What metabolic pathways that supply ATP in muscle fibres exist?
Transfer of high energy phosphate from creatine Phosphate to ADP (immediate ATP source), oxidative phosphorylation (main source when O2 present), Glycolysis (main when O2 not present)
What are the 3 types of skeletal muscle fibres?
Slow-Oxidative (I), Fast-Oxidative (IIa) and Fast-Glycolytic (IIx)
Where does the motor neurone axon divide into unmyelinated branches in the innervation of skeletal muscle?
Near to the muscle
What does each motorneurone branch innervate in skeletal muscle?
An individual muscle cell (muscle fibre)
What do fine branches in skeletal muscle end in?
A terminal bouton that forms a chemical synapse with the muscle membrane at the NMJ
How are action potentials in the muscle cell body conducted?
Via the axon to the boutons causing the release of ACh
What are the key features of the skeletal NMJ?
Terminal bouton (and surrounding Schwann cell), synaptic vesicles, synaptic cleft and end plate region of membrane (sarcolemma) thrown into series of junctional folds
At what zone do synaptic vesicles at the skeletal NMJ await release?
Where are nicotinic ACh receptors located in skeletal NMJ?
Regions of the junctional folds that face away from the active zones
Describe the pre-synaptic processes in the terminal bouton
Choline transported into terminal by choline transporter (symport with Na+). ACh is synthesized in cytosol from choline and acetylCoA by ChAT. ACh is concentrated in vesicles by vesicular ACh transporter. Arrival of action potential at terminal causes-depolarization/opening of Ca2+ channels, allows Ca2+ entry. Ca2+ causes docked vesicles at active zones to fuse with presynaptic membrane (exocytosis)-ACh diffuses into cleft to activate post-synaptic nicotinic ACh receptors in endplate region
How are nicotinic ACh receptors assembled in the end-plate?
As a pentamer of glycocprotein subunits that surround a central, cation selective, pore (5 M2 helices). Pore contains a gate that is closed, unless two molecules ACh bind to exterior of receptor.
What is the open channel of the nicotinic ACh receptor permeable too?
Roughly equally permeable to Na+ and K+, but does not conduct anions
What happens when the gate of the nicotinic ACh receptor is open?
Na+ enters the muscle cell (influx) whilst K+ exits (efflux) simultaneously through many receptors at end plate.
How is the depolarization known as end plate potential generated?
Because driving force for Na+ > K+ at resting membrane potential, influx of Na+>efflux of K+
What is the electrical response to one quantum of transmitter due to activation of nicotinic ACh receptors at the end plate?
Miniature end plate potential
How much ACh do each vesicle contain?
What do many m.e.p.p.s summate to produce?
End plate potential- a graded (electrotonic) response
What does an epp that exceeds threshold trigger?
An all or none propagated action potential that initiates contraction
What does one action potential in the motor nerve normally trigger?
One ap in the muscle (one to one coupling) and a subsequent twitch (contraction) of muscle
How do drugs or toxins that reduce amplitude of epp so that it dos not reach threshold for opening of Na+ channels work?
Block neuromuscular transmission as this means no muscle ap is generated
Why is muscle action potential required for contraction?
Muscle fibre with voltage activated Na+ channels- an ap propagates from endplate over the length of the muscle fibre
How does the muscle action potential cause contraction by release of Ca2+ from intracellular stores?
Ap propagates over sarcolemma of fibre and enters T-tubules (close to SR). Ap at T-tubule triggers release of Ca2+ from SR (Ca2+ store) which causes contraction by interacting with troponin associated with myofibrils
How does termination of the action of ACh occur?
Result of hydrolysis of ACh by AChE, enzyme associated with end plate membrane. AChE hydrolyses ACh to choline and acetate, former taken up by choline transporter. Latter diffuses from synaptic cleft.
Is AChE efficient?
Extremely- hydrolysis of some ACh molecules occur even prior to transmitter binding to receptors, once unbinding occurs virtually all molecules hydrolysed, limiting rebinding and terminating epp within a few ms
What is the physiological cause of neuromyotonia?
AI condition-antibodies against voltage activated K+ channels in motor neurone disrupt function resulting in hyperexcitability
What is the physiological cause of LEMS?
AI origin- antibodies against Ca2+ channels in motor neurone terminal result in reduced Ca2+ entry in response to depolarization and hence reduced vesicular release of ACh
What is the physiological cause of Myasthenia Gravis?
AI origin usually- antibodies against nicotinic ACh receptors in endplate result in reduction in number of functional channels and hence amplitude of epp
How does botulinum toxin physiologically work?
Acts at motor neurone terminals to irreversibly to inhibit ACh release. Modifies proteins involved in docking of ACh vesicles
What is the physiological action of 'curare-like'compounds?
Interfere with postsynaptic action of acetylcholine by acting as competitive antagonists of nicotinic ACh receptor. Reduce amplitude of e.p.p to below threshold
What is the difference between simple and compound synovial joints?
Simple is one pair of articular surfaces, compound is more than one
What is the role of joints during purposeful motion?
Stress distribution and confer stability
What is joint lubrication provided by?
Cartilage interstitial fluid
Synovium - derived hyaluronic acid (mucin) - a polymer of disaccharides
Synovium-derived lubrcin - a glycoprotein
What are the functions of synovial fluid?
Lubrication, reduces friction, helps minimize wear and tear, aids in nutrition of articular cartilage, supplies chondrocytes with O2/nutrients and removes CO2/waste products
Is the synovial fluid a static poole?
No-continuously replenished and absorbed by the synovial membrane
What is hyaluronic acid (mucin) produced by in synovial joints?
What happens to the viscosity and elasticity of synovial fluid during joint movement?
What is rapid movement associated with in terms of viscosity and increased elasticity?
Decreased viscosity and increased elasticity
What is the appearance of normal synovial fluid?
Clear and colourless
What is the WBC count in synovial fluid, and polymorph?
What can cause the synovial fluid WCC to increase?
Inflammatory and septic arthritis
When does the synovial fluid turn red?
In traumatic synovial tap and in haemorrhagic arthritis
What is the clarity of normal, inflammatory and septic synovial fluid?
Colourless-straw to yellow-variable
What are the main functions of articular cartilage?
Provides a low friction lubricated gliding surface. Distributes contact pressure to subchodral bone
What plays a significant role in determining the mechanical properties of cartilage?
The composition of cartilage ECM and the interaction between fluid and solid phase
How do zones of articular cartilage differ?
Organisation of collagen fibres and relative content of cartilage components
What kind of cartilage is the articular cartilage usually?
What is the ECM of articular cartilage made of?
Water (70%), collagen (20%)- mainly type II contributes most to elastic behavior of cartilage, and proteoglycans (10%)
Describe the mechanical properties of the cartilage component water
Unevenly distributed, ~80% near articular surface. Decreases with age. Maintains resiliency of tissue and contributes to nutrition/lubrication system
Describe the mechanical properties of the cartilage component water
Mainly type II collagen, decreases with age. Maintains cartilage architecture. Provides tensile stiffness and strength
Describe the mechanical properties of the cartilage component proteoglycan
Highest conc found in middle/deep zone. Composed mainly of glycosaminoglycan e.g. chondroitin sulphate. Composition decreases with age - chondroitin decreases with age. Responsible for compressive properties associated with load bearing
What is the ECM synthesised, organized, degraded and maintained by?
Is the articular cartilage vascular or avascular?
In normal joints how can the rate of ECM degradation be compared with the rate it is replaced?
Rate of degradation doesn't exceed rate of replacement
What breaks down the ECM components of cartilage?
Metalloproteinase proteolytic enzymes e.g. collagenase and stromelysin
What do catabolic factors of cartilage matrix turnover do, and what are examples of these?
Stimulate proteolytic enzymes and inhibit proteoglycan synthesis
Tumour necrosis factor (TNF)-alpha
What do anabolic factors of cartilage matrix turnover do, and what are examples of these?
Stimulate proteoglycan synthesis and counteract effects of IL-1
Tumour growth factor (TGF)-β
Insulin-like growth factor (IGF)-1
What do the levels of serum and synovial keratin sulphate indicate regarding cartilage?
Increased indicates cartilage breakdown-occurs with age and patients with osteoarthritis
What does the level of type II collagen in synovial fluid indicate regarding cartilage?
Increased indicates cartilage breakdown-useful in evaluating cartilage erosion e.g. in osteoarthritis and rheumatoid arthritis
What does synovial cell proliferation and inflammation cause?
What can deposition of salt crystals such as uric acid cause in a joint?
What is pain?
An unpleasant sensory and emotional experience, associated with actual tissue damage or described in terms of such damage
What are the 3 forms of pain?
Nociceptive and inflammatory (adaptive) and pathological (maladaptive)
What are nociceptors?
Specific peripheral primary sensory afferent neurons normally activated preferentially by intense stimula (e.g. thermal, mechanical, chemical), that are noxious. They are first order neurons that relay info to second order in CNS by chemical synapse transmission
What is nociceptors adaptive ability and threshold?
Is adaptive-serves as early warning system to detect and minimize contact with damaging stimuli. High threshold- only intense stimuli activate nociceptors
What does nociceptive pain do to most other ongoing activities of nervous system?
Overrides most others
What reflex does nociceptive pain initiate?
What causes inflammatory pain?
Activation of the immune system in injury or infection-is adaptive and protective
What does inflammatory pain cause?
Pain hypersensitivity (heightened sensitivity to noxious stimuli) and allodynia (innocuous stimuli now elicit pain)
What does inflammatory pain assist in?
Healing of a damaged body part-discourages physical contact and movement.
What is pathological pain's adaptive capability?
Is maladaptive with no protective function-results from abnormal nervous system function-may be neuropathic, or dysfunctional
What are the subtypes of nociceptor?
A delta-fibres, and C fibres
What are A delta fibres?
Mechanical/thermal nociceptoes that are thinly myelinated (6-30m/s)-respond to noxious stimuli. Mediate 'first', or fast, pain
What are C fibres?
Nociceptors that are unmyelinated (0.5-2m/s)-collectively they respond to all noxious stimuli. Second, or slow, pain
What peripheral terminal of polymodal nociceptors is activated by thermal stimuli?
Members of transient receptor potential (TRP) family, particularly TRPV1 activated by noxious heat.
What peripheral terminal of polymodal nociceptors is activated by chemical stimuli?
H+ activates acid sensing ion channels (ASICs), ATP activates P2X/Y receptors, bradykinin activates B2 receptors
What does a stimulus do in terms of nerve terminals?
Opens ion channels to elicit a depolarizing receptor (or generator) potential
What are the characteristics of the amplitude of generator potential?
It is graded and proportional to stimulus intensity
How is the afferent function of C-fibre peptifergic polymodal nociceptors involved in the transmission of pain?
Transmit nociceptive information to the CNS via release of glutamate and peptides (substance P, neurokinin A) within the dorsal horn
How is the efferent function of C-fibre peptifergic polymodal nociceptors involved in the transmission of pain?
Release pro-inflammatory mediators [e.g. calcitonin gene-related peptide (CGRP), substance P] from peripheral terminals – contributes to neurogenic inflammation
What does long term noxious stimulation cause?
Increased spinal excitability contributing to hyperalgesia and allodynia
What occurs in neurogenic inflammation?
Peptides (SP/CGRP) released from free nerve ending of peptidergic nociceptor due to damage, or inflamm mediators. SP causes -vasodilation/extravasation of plasma protein (promotes bradykinin/prostaglandins formation), release of histamine, sensitised surrounding nociceptors. CGRP induces vasodilation. 1'/2' hyperalgesia and allodynia ensue
In the neurotransmission between the primary afferent and second order neurone in the dorsal horne, what is the primary neurotransmitter?
What does glutamate do in the projection neurone in dorsal horn?
Produces fast epsp and neuronal excitation by activating primarily postsynaptic AMPA receptors with NMDA receptor participation
What do peptides (substance P and CGRP) do in projection neurone in dorsal horn?
Cause a slow prolonged epsp that facilitates activation of NMDA receptors by relieving voltage-dependent block by Mg2+
What occurs in the projection neurone of dorsal horn when glutamate is transmitted from primary afferent?
Activation of glutamate receptors>membrane depolarization>opening of voltage gated Na+ channels> action potential
Where are primary afferent cell bodies (apart from trigeminal system) located?
Dorsal root ganglia
Where does the axon of primary afferent bodies terminate?
Centrally in dorsal horn of spinal cord in various laminae of Rexed
Where do nociceptive C and A delta fibres mostly terminate?
Superficially in laminae I and II (also V for A delta)
What do nociceptive specific cells only synapse with?
C and A delta fibres
What are cells that only receive input from A beta fibres?
What do wide dynamic range neurons receive input from?
All 3 types of nociceptive fibre, so respond to wide range of stimuli
What tracts of second order neurons ascend the spinal cord in the anterolateral system mainly?
Spinothalamic tract (STT), Spinoreticular Tract (SRT)
In the STT where do projection neurons originating from lamina I (fast fibre A delta pain) terminate?
In posterior nucleus of thalamus
In the STT where do projection neurons originating from lamina V (WDR neurones) terminate?
In posterior and ventroposterior nucleus of thalamus
What does the SRT largely transmit?
Slow C fibre pain
What does the SRT make extensive connections with?
Reticular nuclei in brain stem (e.g. periaqueductal grey (PAG) and parabrachial nucleus (PBN))