Physiology Flashcards
Which of the 3 types of muscles are striated?
Striated: skeletal and cardiac muscle
Unstriated: smooth muscle
Striation appears as alternating dark and light bands under the microscope. What makes up the light and dark bands?
Dark bands - myocin thick filaments
Light bands - actin thin filaments
Which ion links excitation and contraction?
Ca2+
Where does the Ca2+ involved in skeletal muscle vs cardiac muscle contraction come from?
Skeletal - entirely from the sarcoplasmic reticulum
Cardiac - ECF and sarcoplasmic reticulum
State what controls the strength of contraction in skeletal muscle (2) vs cardiac muscle (1)
Skeletal - motor unit recruitment and summation of contractions
Cardiac - preload
Skeletal muscles are arranged into…
Motor units
What are motor units?
A number of muscle fibres innervated by a single alpha motor neuron
What is the neurotransmitter at skeletal muscle neuromuscular junctions?
Acetylcholine
A muscle which requires precision more than power (e.g., the hand) has more/fewer muscle fibres per motor unit
Fewer (~10)
A muscle which requires power more than precision (e.g., the thigh) has more/fewer muscle fibres per motor unit
More (100s - 1000s)
Skeletal muscle fibres usually extend the entire length of muscle. T/F
True
Skeletal muscles are attached to bone by…
Tendons
A singular muscle fibre (cell) is made up of many…
Myofibrils
Myofibrils contain X and Y arranged into Z
X - actin
Y - myosin
Z - sarcomeres
The functional unit of skeletal muscle is…
the sarcomere
What are the 4 zones of the sarcomere called?
A-band
H-zone
M-line
I-band
Describe each sarcomere zone: A-band H-zone M-line I-band
A-band: area of actin and myosin overlap
H-zone: area in the middle of the A-band where thin filaments don’t reach
M-line: vertical line down the middle of the A-band and H-zone
I-band: initial portion of thin filaments that do not project into A-band i.e., do not overlap thich filaments
How is muscle tension produced?
The ATP-dependent sliding of actin filaments over myocin filaments
How does ATP aid skeletal muscle contraction and relaxation?
Contraction - broken down into ADP and Pi which energises myosin
Relaxation - releases the actin-myosin cross-bridge and pumps Ca2+ back into the sarcoplasmic reticulum
Why does rigor mortis occur when someone dies?
ATP is depleted to Ca2+ can no longer be pumped back into the sarcoplasmic reticulum and so the muscles stay contracted
Describe release of Ca2+ from the sarcoplasmic reticulum in skeletal muscle
The surface action potential spreads down the transverse (T)-tubules of the sarcoplasmic reticulum, causing it to release Ca2+ from its lateral sacs
Once myosin is energised by ATP, why is Ca2+ required to form the actin-myosin cross-bridge?
Ca2+ binds to troponin and moves the troponin-tropomyosin complex out of the myosin binding site on actin
Energised myosin can then bind to actin and form the cross-bridge
Summarise the process of excitation-contraction coupling in skeletal muscle (7)
- ACh released across neuromuscular junction
- ACh binds and causes an action potential to propegate along the surface membrane
- The action potential travels down the T-tubules of the sarcoplasmic reticulum and triggers Ca2+ release from the lateral sacs
- Ca2+ binds to troponin on actin filaments, pulling the troponin-tropomyosin complex out of the way to allow the actin-myosin cross bridge to form
- Myosin pulls actin towards the centre of the sarcomere using energy from ATP
- When there is no longer a local action potential, Ca2+ is actively taken back up by the sarcoplasmic reticulum
- With Ca2+ no longer bound to troponin, the troponin-tropomyosin complex blocks the binding site on actin again, and so actin slips back and contraction ends
What 2 factors influence the tension developed by skeletal muscle?
- The number of muscle fibres/motor units contracting within the muscle
- Tension developed by each contracting muscle fibre
How is tension (force of contraction) increased in skeletal muscle?
By increasing the frequency of action potential stimulation
The duration of action potential in skeletal muscle is much shorter/longer than the duration of the resulting muscle twitch
Shorter
Why does increasing the frequency of action potentials increase muscle tension/force of contraction?
When another action potential is fired before the muscle has time to relax from the previous stimulation, the second response is added to the first and a greater muscle tension is developed (= summation of contractions)
What is meant be ‘tetanus’ when referring to skeletal muscle contraction?
The maximal sustained contraction caused by twitch summation
What prevents tetanic contraction in cardiac muscle?
The long refractory period
Maximum tetanic contraction can be achieved when the muscle is at optimal muscle length (usually resting length). Why is this?
This is the optimum length for actin-myosin cross bridge formation
What are the 2 types of skeletal muscle contraction?
- Isotonic contraction
- Isometric contraction
Describe isotonic contraction and when it is used
- Muscle tension remains constant while muscle length changes
- Used for body movements and moving objects
Describe isometric contraction and when it is used
- Muscle tension develops at constant muscle length
- Used for supporting objects in fixed positions and maintaining body posture
What are the main differences between the 3 different types of skeletal muscle fibres? (3)
- The enzymatic pathways for ATP synthesis
- Resistance to fatigue (depends on capacity to synthesise ATP)
- Activity of myosin ATPase (enzyme which controls the speed of the cross-bridge cycle in contraction)
Each motor unit usually contains one/multiple type(s) of muscle fibres
One type
What are the 3 pathways for ATP synthesis?
- Oxidative phosphorylation in mitochondria (main source when O2 present)
- Pi from creatine phosphate to ADP (immediate source of energy)
- Glycolysis (when O2 not present)
What are the 3 pathways for ATP synthesis?
- Oxidative phosphorylation in mitochondria (main source when O2 present)
- Pi from creatine phosphate to ADP (immediate source of energy)
- Glycolysis (when O2 not present)
What are the 3 types of skeletal muscle fibres?
Type I - Slow Oxidative
Type IIa - Fast Oxidative
Type IIb - Fast Glycolytic
Describe resistance to fatigue, capacity to synthesise ATP and speed of contraction in the 3 types of skeletal muscle fibres
Slow Oxidative Type I - highly resistant to fatigue, high capacity to synthesise ATP, slow in speed
Fast Oxidative Type II1 - medium resistance to fatigue, medium capacity to synthesise ATP, medium speed
Fast Glycolytic Type IIb - low resistance to fatigue, low capacity to synthesise ATP, fast in speed
Describe what activities the 3 different types of skeletal muscle fibres are used for
Slow Oxidative Type I - prolonged, low work aerobic activities e.g., maintaining posture, walking
Fast Oxidative Type IIa - aerobic and anaerobic metabolism and prolonged, moderate work activities e.g., jogging
Fast Glycolytic Type IIb - anaerobic metabolism and short term high intensity activities e.g., jumping
Where does the motor unit receive inputs from?
The brain and a variety of receptors e.g., withdrawl reflex, stretch reflex
The simplest forms of coordinated movement are called…
Reflex actions
What is a reflex action?
A stereotyped response to a specific stimulus
Describe the stretch reflex arc
- The muscle spindle is the sensory receptor that is activated by muscle stretch
- Stretching the muscle spindle increases firing in the afferent neurons
- The afferent neurons synapse in the spinal cord with the alpha motor neurons that innervate the stretched muscle
- This results in contraction of the stretched muscle
Why are tendon reflexes of clinical use?
Reflexes help localise a lesion in the nervous system
e.g., a problem with the knee jerk reflex would suggest a problem with spinal nerves L3 and L4 or the femoral nerve
What are muscle spindles and where are they found?
The sensory receptors for the stretch reflex
They are found within the belly of muscles
Muscle spindles are referred to as intrafusal/extrafusal fibres
Intrafusal
How do muscle spindle fibres run relative to ordinary muscle fibres?
They run parallel to ordinary muscle fibres (extrafusal fibres)
What are the sensory nerve endings in muscle spindles called?
Annulospiral fibres
What are the efferent neurons that supply muscle spindles called?
Gamma motor neurons
Contraction of muscle spindles contributes to the overall strength of muscle contraction. T/F
False
What 4 factors can lead to impairment of skeletal muscle function?
- Intrinsic muscle disease
- Neuromuscular junction disease
- Disease of lower motor neurons which supply the muscle
- Disruption of input to motor nerves e.g., upper motor neuron disease
List some causes of intrinsic muscle disease (5)
- Congenital myopathies
- Inflammatory myopathies
- Non-inflammatory myopathies e.g., fibromyalgia
- Endocrine myopathies e.g., Cushing syndrome
- Toxic myopathies e.g., alcohol, statins
List 4 symptoms of muscle disease
- Muscle weakness/tiredness
- Delayed relaxation after voluntary contraction (myotonia)
- Muscle pain (myalgia)
- Muscle stiffness
List 5 investigations used in neuromuscular disease
- Electromyography (EMG) (electrodes detect the presence of muscle activity)
- Nerve conduction studies
- Muscle enzymes e.g., creatine kinase (CK)
- Inflammatory markers e.g., CRP
- Muscle biopsy
What are the 3 types of joint in the human skeleton?
Fibrous
Cartilaginous
Synovial
Describe fibrous joints
- Bones are united by fibrous tissue
- Doesn’t allow any movement (synarthrosis)
- e.g., bones of the adult skull
Describe cartilaginous joints
- Bones are united by cartilage
- Allow limited movement (amphiarthrosis)
- E.g., intervertebral discs, pubic symphsis, costochondral joints
Describe the structure of a synovial joint
- Bones are separated by a cavity (which contains synovial fluid) and united by a fibrous capsule
- The articular surfaces of the bones are covered with hyaline cartilage
- The inner aspect of the fibrous capsule is lined with synovial membrane
What makes up the synovial membrane?
- Vascular connective tissue
- Capillary networks
- Lymphatics
- Synovial cells (fibroblasts)
How is the synovial fluid produced?
By synovial cells (fibroblasts) in the synovial membrane
How are synovial joints classified? (2 groups)
Simple synovial joint - one pair of articular surfaces e.g., digit joints
Compound synovial joint - more than one pair of articular surfaces e.g., elbow joint
As well as the fibrous capsule, what extra-articular structures support the joint? (3)
Ligaments
Tendons
Bursae
What are the functions of the synovial fluid in the synovial cavity? (3)
- Lubricates the joint so minimises wear-and-tear
- Reduces friction so facilitates movement
- Supplies chondrocytes with O2 and nutrients and removes CO2 and waste products (as the articular cartilage is avascular)
-
Synovial fluid is static in the synovial cavity. T/F
False
The synovial fluid is continuously replenished and absorbed by the synovial membrane
Describe the synovial fluid viscosity
- High viscosity due to hyaluronic acid (mucin) produced by synovial cells
- Viscosity varies with joint movement
Describe changes in viscosity and elasticity of synovial fluid during rapid movement (in a normal joint)
Viscosity decreases
Elasticity increases
Compare the colour, total WCC and polymorph count in normal vs inflammatory vs septic synovial fluid
Normal: colourless, WCC <200, PMN count <25
Inflammatory: translucent, WCC 2,000-75,000, PMN count often >50
Septic: opaque, WCC often >100,000, PMN count often >75
When might synovial fluid be red?
- Trauma
- Haemorrhagic arthritis
What are the 3 main functions of the articular hyaline cartilage?
- Prevents wear-and-tear of joints by providing a low friction, lubricated surface
- Distributes contact pressure to subchondral bone
- Composition of the ECM determines the mechanical properties of the cartilage
What are the 4 zones of articular cartilage and which one is the largest?
(articular surface)
- Superficial zone (10-20%)
- Middle zone (40-60% -> largest zone)
- Deep zone (30%)
- Calcified zone
(subchondral bone)
What are the mechanical properties of water in the articular cartilage?
- Maintains the resilience of the tissue
- Contributes to nutrition and lubrication (most water is found near the articular surface)
What are the 4 zones of articular cartilage and which one is the largest?
(articular surface)
- Superficial zone (10-20%)
- Middle zone (40-60% -> largest zone)
- Deep zone (30%)
- Calcified zone
(subchondral bone)
Describe the composition of the ECM of the articular cartilage (3)
Water (70%)
Collagen (20%)
Proteoglycans (10%)
What are the mechanical properties of collagen in the articular cartilage?
- Maintains the cartilage architecture
- Provides tensile stiffness and strength
What are the mechanical properties of proteoglycans in the articular cartilage?
- Responsible for the compressive properties associated with weight bearing
What proportion of the total cartilage volume is made up of ECM?
What makes up the rest of the <2%?
> 98%
Chondrocytes
What changes may occur in diseased articular cartilage? (2)
- Changes in the relative amounts of the 3 major articular cartilage components (water, collagen & proteoglycans)
- If the rate of ECM degradation exceeds the rate of its synthesis
List 4 processes that may result in a diseased joint
- Cartilage and synovial deterioration due to ageing and wear-and-tear (e.g., osteoarthritis)
- Synovial cell inflammation and proliferation (e.g., rheumatoid arthritis)
- Deposition of salt crystals (e.g., uric acid in gout)
- Injury and inflammation to periarticular structures (e.g., tendonitis)
What effects may be seen in subchondral bone following cartilage wear-and-tear?
- Cyst formation
- Sclerosis (abnormal hardening of tissue)
- Osteophyte formation
Define pain
An unpleasant sensory and emotional experience associated with tissue damage
Chronic pain is usually pain that lasts for…
> 3 months
Name the 4 distinct processes in the physiology of pain
- Transduction
- Transmission
- Modulation
- Perception
Describe the 4 processes of pain physiology:
- Transduction
- Transmission
- Modulation
- Perception
- Transduction: peripheral nociceptor translates noxious stimulus into electrical activity
- Transmission: pain signal is propagated through the nervous system as nerve impulses
- Modulation: pain transmission is modified/hindered in the nervous system e.g., by inhibitory neurotransmitters like endogenous opioids
- Perception: the conscious experience of pain which causes physiological and behavioural responses
What are nociceptors?
Free nerve endings that are located all over the body and respond to pain caused by noxious stimuli e.g., mechanical, thermal or chemical
What type of neurones are nociceptors?
Primary sensory afferent
What order of neurone is a nociceptor?
First order
Once the nociceptor has been triggered by a noxious stimulus, what happens in the neuron?
Depolarisation occurs and an AP spreads along the axon to second order neurones in the CNS
Describe the nociceptive pathway from a peripheral site to the spinal cord and then to the brain
- Free nerve endings (first order neurones) are depolarised and pass information to second order neurones in the spinal cord via neurotransmitters
- Second order neurones ascend the spinal cord in the anterolateral system
- The signal is passed to third order neurones in the thalamus
- Third order neurones relay the information to the primary sensory cortex
Name the 2 tracts involved in the anterolateral system that takes second order neurones up the spinal cord.
Briefly state what aspect of pain they are involved in
- Spinothalamic tract (STT) - involved in perception of pain intensity and location
- Spinoreticular tract (SRT) - involved in autonomic responses to pain, arousal and emotional responses
Where are the cell bodies of first, second and third order neurones found?
First: dorsal root ganglion of spinal nerves
Second: posterior horn of spinal cord
Third: thalamus
Name the 2 subtypes of nociceptors
Alpha-delta fibres
C fibres
Describe the types of pain that each of the subtypes of nociceptor is involved in
A-delta fibres: the immediate sharp pain felt in response to noxious stimuli
C fibres: the second, duller pain remaining after the initial insult
Why do A-delta fibres mediate faster pain responses than C fibres?
A-delta fibres are myelinated so conduction velocity is fast
C fibres are unmyelinated so conduction velocity is slower
Name the 3 types of pain
- Nociceptive
- Inflammatory
- Pathological
Describe nociceptive pain
Nociceptors are provoked by noxious stimuli which are damaging the tissues
Describe inflammatory pain
The immune system is activated to release mediators by tissue injury or infection
This results in heightened pain sensitivity in the affected area
Inflammatory pain causes hyperalgesia and allodynia. What is meant by these terms?
Hyperalgesia = heightened pain sensitivity to noxious stimuli
Allodynia = pain sensitivity to innocuous stimuli
What are the 2 subtypes of pathological pain?
Neuropathic
Dysfunctional
Describe neuropathic pathological pain
Poorly localised shooting pain or numbness caused by damage to neural tissue
e.g., compression neuropathies, peripheral neuropathies
Describe dysfunctional pathological pain
Pain with no identifiable damage or inflammation
e.g., fibromyalgia, IBS
Which of the 3 types of pain are adaptive and why?
Nociceptive pain - it gives a quick warning to remove the noxious stimulus
Inflammatory pain - promotes repair by discouraging physical contact and movement of the affected area
Why is pathological pain maladaptive?
It occurs in the absence of ongoing noxious stimuli, so is not protective, and does not promote repair
What is referred pain?
Referred pain = deep or visceral pain felt in an area of skin which is distant from the internal organ where the pain originated
Why does referred pain occur?
When nociceptive visceral afferents and skin afferents converge on the same spinothalamic neurons at the same spinal level
Where might pain from the... - Liver - Gallbladder - Diaphragm/lungs - Heart - Stomach/ pancreas - Appendix ... be referred to?
- Liver: right side of neck
- Gallbladder: right shoulder
- Diaphragm/lungs: left shoulder
- Heart: left arm and jaw
- Stomach/ pancreas: centre of abdomen
- Appendix: umbilicus