Flashcards in Physiology & Pharmacology Deck (75):
Which nervous system innervates skeletal muscle?
Which nervous system innervates cardiac and smooth muscle?
What is a motor unit?
A single alpha motor neurone and all of the skeletal muscle fibres it innervates
Do muscles of precision have more or fewer motor units than muscles of power?
What is the different levels of organisation in skeletal muscle?
Whole muscle (organ) > Muscle fibre (cell) > Myofibril > Sarcomere (functional unit) > Made up up of myosin nd actin filaments (cytoskeletal elements)
What is the different between skeletal and cardiac muscle in terms of initiation and propagation of contraction?
Skeletal muscle has a neurogenic initiation of contraction from motor units, with NMJs present. While cardiac muscle is a myogenic (pacemaker potential) initiation of contraction, with no NMJs but gap junctions present
**How is Ca2+ released and used in excitation/contraction coupling in skeletal muscle?
1) ACh is released from the motor unit at the NMJ which generates an AP 2) AP is then propagated across the surface membrane on the muscle cell and down T tubules in the muscle 3) This triggers Ca2+ release from lateral sacs of the sarcoplasmic reticulum 4) These Ca2+ bind onto troponin on actin filaments, causing tropomyosin to be physically moved to uncover cross-bridge binding sites on actin 5) Myosin cross-bridges bind onto actin, pulling the actin filament closes to the centre of the sarcomere using ATP 6) Ca2+ then actively taken up by the SR when AP ends 7) This means the tropomyosin slips back and blocks the binding site
True or false: Skeletal muscles fibres (cells) span the entire length of the muscle
Which filaments and thin and light, and which are dark and thick?
Actin = thin and light
Myosin = thick and dark
Which lines bind a sarcomere?
**What is the A band?
Made up of thick filaments along with portions of overlapping thin filaments
** What is the H zone?
The lighter area in the middle of the A band where thin filaments don't reach
**What is the M line?
Extends vertically down the A band within the centre of the H zone
**What is the I band?
Remaining portion of thin filaments that do not project into the A band
True or false: ATP is needed in both contraction and relaxation
What 2 things does gradation (strength) of muscle contraction depend on?
1) Number of muscle fibres contracting 2) Tension of each contracting fibre
Motor unit recruitment
A stronger contraction can be achieved by stimulation of more motor units
What does the tension developed by each muscle fibre depend on?
1) Frequency of stimulation
2) Summation of contractions (multiple twitches via repeated APs)
3) Length of muscle fibre at onset of contraction
4) Thickness of muscle fibre
What is twitch summation?
If a muscle fibre is restimulated before it has completely relaxed, the second twitch is added on to the first twitch. This is possible because APs are shorter than their resulting twitch, so APs can be repeated. This is required for movement, as a single twitch is not useful for bringing around movement
What is tetanus?
If a muscle fibre is stimulated so rapidly that is does not have an opportunity to relax at all between stimuli, a maximal sustained contraction occurs
What are the contractile and elastic components of skeletal muscle contraction?
Contractile - cross bridge cycling
Elastic - stretching and tightening of muscle CT and tendon
Muscle tension remains the same as muscle length changes eg. lifting things
Muscle tension develops at constant muscle length eg. holding arms up or pushing against heavy objects
What are the 3 main sources of ATP to skeletal muscle?
- Transfer of high energy phosphate from creatine Phosphate to ADP - (immediate source)
- Oxidative phosphorylation (main source when O2 is present)
- Glycolysis (main source when O2 is not present)
When are Type I (slow-twitch fibres) used?
For prolonged relatively low work aerobic activities e.g. maintenance of posture, walking
When are Type II (intermediate-twitch fibres) used?
Use both aerobic and anaerobic metabolism and are useful in prolonged relatively moderate work activities e.g. jogging
When are Type III (fast-twitch fibres) used?
Use anaerobic metabolism and are mainly used for short-term high intensity activities e.g. jumping
What is a reflex?
A stereotyped response to a specific stimulus
What is a stretch reflex?
A negative feedback that resists passive change in muscle length to maintain optimal resting length of muscle
How does the stretch reflex work?
1) Muscle spindle is the sensory receptor which detects stretch
2) Stretch here increases firing in afferent neutrons
3) These neutrons synapse at SC with alpha motor neurone of the stretched muscle
4) These cause the contraction of the muscle, and relaxation of antagonist muscle
What are annulospiral fibres?
Sensory nerve endings in muscle spindles
What are the efferent neutrons which supply the muscle spindles called?
Gamma (g) motor neurons
What 4 things can cause impairment of muscle function?
1) Intrinsic disease of muscle
2) Disease of NMJ
3) Disease of lower motor neurone which supply the muscle
4) Disruption of input to motor neurone
What investigations are useful for neuromuscular disease?
1) Electromyography (EMG) - electrodes detect presence of muscular activity
2) Nerve conduction studies (determines functional integrity of peripheral nerves)
3) Muscle enzymes (eg. creatinine kinase)
**What are the key features of a skeletal NMJ?
(1) the terminal bouton (and surrounding Schwann cell);
(2) synaptic vesicles;
(3) the synaptic cleft and (4) the end plate region of the muscle cell membrane (sarcolemma) thrown into a series of junctional folds
What is the role of Ca2+ and ACh in the NMJ transmission?
On arrival of the AP, Ca2+ enters the terminal through voltage gated channels, causing the release of ACh from vesicles. Each then diffuses into synaptic cleft, and activates nicotinic receptors on the postynamptic membrane - which allows influx of Na and efflux K+ causing end plate potential
How to miniature end-plate potentials cause muscle APs?
Many m.e.p.ps summate to produce the end-plate potential (e.p.p) a graded (electrotonic) response. An e.p.p that exceeds threshold triggers an ‘all or none’ propagated action potential that initiates contraction (usually one muscle twitch per AP).
What are miniature end-plate potentials (e.p.p)?
Each vesicle contains a ‘quantum’ of neurotransmitter (ACh).
The electrical response to one quantum of transmitter, due to the activation of nicotinic ACh receptors at the endplate, is a miniature endplate potential (m.e.p.p)
How does the muscle AP cause contraction?
Action potential propagates over the surface membrane (sarcolemma) of skeletal muscle fibre and enters transverse (T) tubules. Action potential arriving at the T-tubule triggers release of Ca2+ from the SR which in turn causes contraction by interacting with troponin associated with the myofibrils
What role does acetylcholinesterase (AChE) play?
Rapid termination of neuromuscular transmission via hydrolysis of ACh
What are the 3 forms of pain?
1) Nociceptive pain, Inflammatory pain and pathological pain
Pain resulting from stimulation of nociceptors by noxious stimuli e.g. thermal, mechanical, chemical
Of the 3 forms of pain, which are adaptive and which are maladaptive?
Nociceptive and inflammatory are adaptive, while pathological is maladaptive
What is the purpose of nociceptive pain?
Serves as an early warning system to detect and minimise contact with damaging stimuli, initiating withdrawal reflexes and inscribe memories that allows avoidance in the future
What 2 additional symptoms occur as a result of inflammatory pain?
Pain hypersensitivity (heightened sensitivity to noxious stimuli) and allodynia (innocuous stimuli now elicit pain)
How does inflammatory pain aid in the healing a damaged body part?
• Discourages physical contact (e.g. a wound)
• Discourages movement (e.g. an inflamed joint)
What is pathological pain?
Is maladaptive with no protective function - results from abnormal nervous system function - may be neuropathic, or dysfunctional
What is congenital insensitivity to pain (CIP)?
Absence of pain due to loss of function mutations in the gene SCN9A that encodes a particular voltage-activated Na+ channel that is highly expressed in nociceptive neurones
What kind of fibres are nociceptors?
Primary afferent neurones comprising Aδ- and C-fibres
**What are Aδ fibres?
Mechanical/thermal nociceptors that are thinly myelinated- respond to noxious mechanical and thermal stimuli. Mediate ‘first’, or fast, pain.
**What are C-fibres?
Nociceptors that are unmyelinated – collectively they respond to all noxious stimuli. Mediate ‘second’, or slow, pain
What are peptidergic polymodal nociceptors?
Subset of C-fibres which have afferent and efferent functions: they transmit nociceptive information to the CNS and also release pro-inflammatory mediators from peripheral terminals – contributes to neurogenic inflammation
What is neurogenic inflammation?
Peptides (SP and CGRP) released from free nerve ending of peptidergic nociceptor due to tissue damage, or inflammatory mediators
What is the main neurotransmitter involved in the transmission of pain between primary afferent and second order neutron in dorsal horn?
What are the 2 major nociceptive tracts in the spinal cord?
• The spinothalamic tract (STT)
• The spinoreticular tract (SRT)
What are Synarthrosis joints?
Fibrous joints - joints united by fibrous tissue which don't allow any movement eg. sutures of the skull
What are amphiarthrosis joints?
Cartilaginous joints - united by cartilage which allow limited movement eg. intervertebral discs, pubic symphyses
What are diarthrosis joints?
Synovial joints - separated by a cavity and united by a fibrous capsule and other extra-articular structures
What is the synovial membrane?
Vascular connective tissue layer lining thee inner fibrous capsule, which produces synovial fluid
What is the difference between simple and compound synovial joints?
Simple joints involve one pair of articular surfaces eg. MCP, while compound joints involve more than one eg. elbow
What changes are there in synovial fluid in relation to movement?
Rapid movement is associated with decreased viscosity and increased elasticity (this can fail in a diseased joint e.g. in OA)
What is a normal WBC count of synovial fluid?
<200 WBC/mm3 (this rises in inflammatory and septic arthritis)
**What are the layers of cartilage?
1) Superficial zone 2) Middle zone 3) Deep zone 4) Calcified (then subchondral bone)
What are the 3 main components of cartilage?
Water (70%), collagen (20%) and proteoglycans (10%)
What are catabolic factors of cartilage matrix turnover?
(Stimulate proteolytic enzymes and inhibit proteoglycan synthesis)
• Tumour necrosis factor (TNF)-α
• Interleukin (IL)-1
What are anabolic factors of cartilage matrix turnover?
(Stimulate proteoglycan synthesis and counteract effects of IL-1)
• Tumour growth factor (TGF)-β
• Insulin-like growth factor (IGF)-1
What are markers of cartilage degradation?
Serum and synovial keratin sulphate (Increased levels indicate cartilage breakdown)
and Type II collagen in synovial fluid
(Increased levels indicate cartilage breakdown)
**What are the 2 main functions of different medications in inflammatory arthritis?
Symptom relief vs disease modifiers
What are COX2 inhibitors?
NSAIDs which selectively target cyclooxygenase-2, an enzyme responsible for inflammation and pain (targeting COX-2 selectively reduces the risk of peptic ulceration)
Why is hydroxychloroquine used in connective tissue diseases but not RA?
It has no effect on joint damage
What are biologics?
Drugs designed to target specific aspects of immune system found to be implicated in inflammatory arthritis
What type of drug is allopurinol?
Xanthine oxidase inhibitor
True or False: Allopurinol should be used in acute attacks of gout?
False, it can make acute attacks worse so it is only used in prophylaxis and co-prescribe an anti-inflammatory with it
What should be given to those who cannot tolerate Allopurinol?