VIVA: Physiology - Nerve and muscle cell, and nervous system physiology

Question 1

Draw a skeletal muscle action potential

Answer 1

• need correct shape, axes, resting membrane potentials and durations (+/- 25%)

Question 2

What is the sequence of events in the contraction of a skeletal muscle fibre, starting at the motor-end plate?

Answer 2

6/10 to pass:
1. Activation of voltage-gated Ca2+ channels in presynaptic membrane
2. Ca2+ influx into the cell
3. Exocytosis of preformed ACh into synaptic cleft
4. Diffusion of ACh across synaptic cleft
5. Binding of ACh to post-synaptic nicotinic receptor
6. Increased Na+ and K+ conductance in end-plate membrane of muscle
7. Generation of end-plate potential
8. Generation of action potential in muscle fibres
9. Inward spread of depolarisation along T tubules
10. Release of Ca2+ from terminal cisterns of sarcoplasmic reticulum, and diffusion to thick and thin filaments
11. Binding of Ca2+ to troponin C, uncovering myosin-binding sites on actin
12. Actin-myosin binding and sliding of thin on thick filaments, producing movement

Question 3

What is the sequence of events in the relaxation of a skeletal muscle fibre?

Answer 3

1. Ca2+ pumped back into sarcoplasmic reticulum*
2. Release of Ca2+ from troponin C
3. Cessation of interaction between actin and myosin*

• needed to pass

Question 4

Describe the synthesis of acetylcholine at the neuromuscular junction

Answer 4

1. Acetylcholine is synthesised in the pre-synaptic terminal and stored in synaptic vesicles along with ATP and proteoglycan, until required for synaptic neuronal transmission
2. Acetyl CoenzymeA + choline* is catalysed by the enzyme choline acetyltransferase to form acetylcholine

• needed to pass

Question 5

Once acetylcholine is released into the synaptic cleft, how is its effect terminated?

Answer 5

ACh removed from synaptic cleft by acetylcholinesterase -> broken down into acetate and choline
Choline reuptake into the presynaptic nerve terminal
Acetate to liver and metabolised

Question 6

Draw a nerve action potential and indicate the sequence of events that occur

Answer 6

Dependent on changes in Na+ and K+ conductance:
1. When a depolarising stimulus occurs, the voltage-gated Na+ channels become active and Na+ enters the cell
2. When the threshold potential* is reached, the voltage-gated Na+ channels overwhelm the K+ channels
3. Entry of Na+ causes opening of more voltage-gated Na+ channels and further depolarisation (positive feedback loop), resulting in the upstroke of action potential
4. The membrane potential moves close to the equilibrium potential for Na+ (+60mV)
5. The voltage-gated Na+ channels then enter an inactivated state for a few milliseconds before returning to the resting state
6. Reversal of membrane potential limiting further Na+ influx, and opening of voltage-gated K+ channels results in repolarisation* and end of action potential
7. Slow return of K+ channels results in hyperpolarisation
8. Returns to resting membrane potential

Question 7

Describe the sequence of events that leads to release of acetylcholine at the neuromuscular junction

Answer 7

1. Impulse arrives at the motor neuron ending which causes voltage-gated calcium channels* to open
2. Influx of calcium triggers release of acetylcholine into the synaptic cleft

Question 8

What happens to acetylcholine after release into the synaptic cleft?

Answer 8

1. When vesicle releases ACh into the synaptic cleft, it is rapidly broken down into acetate and choline by the enzyme acetylcholinesterase
2. Choline is actively transported back into the presynaptic terminal to be re-used
3. ACh binds to nicotinic receptors on the motor end-plate leading to Na+ entry and a subsequent depolarising end-plate potential

Question 9

Define resting membrane potential of a neuron

Answer 9

The potential difference* across the cell at rest, with inside negative relative to outside
Normal RMP of a neuron is -70mV

Question 10

Explain how the resting membrane potential of a neuron is generated

Answer 10

The gradients are actively maintained by Na+ / K+ ATPase*
Na+ / K+ ATPase actively pumps Na+ out and K+ into the cell using ATPase for energy
Na+ then passively flows back into the cell via channels down its concentration gradient, and K+ passively flows out of cell via K+ channels down its concentration gradient
At rest, there are more open K+ channels than Na+ channels, so the passive permeability to K+ is greater (hence why RMP of neuron is close to equilibrium potential for K+)

• needed to pass + concept of Na+ in and K+ out with passive flow in opposite direction

Question 11

Why is a cell more excitable in hyperkalaemia?

Answer 11

RMP moves closer to threshold potential for eliciting an action potential (becomes less negative on inside of cell)

Question 12

What factors affect cerebral blood flow?

Answer 12

3/5 to pass:
- MAP at brain level
- MVP at brain level
- ICP
- Viscosity of the blood
- Local constriction/dilatation of cerebral arterioles

Question 13

What is the mechanism of the Cushing response?

Answer 13

Increased ICP results in decreased CBF
Ischaemia of vasomotor centre increases sympathetic nervous system output
BP increases, which stimulates baroreceptors to produce vagal response that decreases HR and RR

Question 14

What is the Monro-Kellie doctrine?

Answer 14

The sum of the volume of blood (75ml), CSF (75ml) and brain (1400g) in the cranium must be relatively constant
An increase in one should cause a reciprocal decrease in either one or both of the remaining two
Negative effects on these therefore if addition intracranial volume (e.g. SDH/EDH) occurs

Question 15

What is the pathogenesis of fever?

Answer 15

2 needed to pass + at least one of toxins and inflammatory pyrogens:
- Bacterial toxins (e.g. endotoxin) act on monocytes, macrophages, and Kupffer cells to produce cytokines that act as endogenous pyrogens
- Inflammatory endogenous pyrogens (IL-1, IL-6, IFN and TNF-a) can be independently produced to cause fever
- Cytokines can also be produced in the CNS and act directly on thermoregulation centres
- Acts on the circumventricular organs (e.g. OVLT) which activates the preoptic area of the hypothalamus causing release of prostaglandins -> resets the homeostatic set point resulting in a fever

Question 16

What is the body’s response to hot and cold environments?

Answer 16

Mechanisms activated by cold* (posterior hypothalamus):
- Increasing heat production: shivering, hunger, voluntary activity, catecholamine release
- Decreasing heat loss: skin vasoconstriction, curling up, piloerection

Mechanisms activated by heat (anterior hypothalamus):
- Decreasing heat production: anorexia, apathy, inertia
- Increasing heat loss: cutaneous vasodilation, sweating, respiration

• need 1 mechanism for each of heat production and loss in hot and cold environment

Question 17

What are upper motor neurons?

Answer 17

Upper motor neurons usually refer to corticospinal neurons that innervate spinal motor neurons* (also includes brainstem neurons that control spinal motor neurons)

• needed to pass

Question 18

What clinical features are seen when upper motor neurons are injured?

Answer 18

Damage initially causes muscles to become weak and flaccid* but eventually leads to spasticity, hypertonia, hyperactive stretch reflexes* and abnormal plantar extensor reflex*

• 2 needed to pass

Question 19

What is the physiological basis of clonus?

Answer 19

Loss of descending cortical input to inhibitory neurons called Renshaw cells, and therefore loss of inhibition of antagonist* muscle groups, resulting in repetitive sequential contractions of ankle flexors and extensors

• needed to pass

Question 20

List the long term complications of spinal cord injury

Answer 20

2 to pass:
- Pressure ulcers
- Protein / muscle degradation
- Hypercalcaemia
- Renal stones (due to hypercalcaemia)
- Urinary tract infection

Question 21

Describe the components of the stretch reflex

Answer 21

Monosynaptic reflex in which skeletal muscle is stretched with contraction of muscle as the response:
- Stretch receptor sensory neuron* makes an excitatory connection with the extensor motor neuron* of the same muscle, and an inhibitory interneuron projecting to the antagonistic muscle
- Sense organ is the muscle spindle, with impulses from the spindle transmitted to the spinal cord by fast sensory fibres passing directly to the motor neurons supplying the same muscle
- Neurotransmitter at the central synapse is glutamate
- Components include sensor (muscle spindle), afferent nerve, integrator (monosynapse on motor neuron), efferent nerve*, effector (intrafusal fibres)

*needed to pass

Question 22

How is the stretch reflex different from the withdrawal reflex?

Answer 22

Withdrawal reflex is a polysynaptic reflex
Also has afferent and efferent limbs, but sensory organ is a nociceptor (responds to painful stimulus), and the central integrator consists of polysynaptic connections in the spinal cord* (i.e. one or more interneurons interposed between afferent and efferent neurons)
Efferent limbs are motor nerves to effector muscles on the ipsilateral and contralateral sides
Results in flexion and withdrawal of the ipsilateral limb*, and extension of the contralateral limb

• needed to pass

Question 23

What is a typical example of a stretch reflex?

Answer 23

Knee jerk response

Question 24

How does the body lose heat?

Answer 24

3 to pass:
- Radiation and conduction, mediated by vasodilation (70%)
- Vaporisation of sweat (27%)
- Respiration (2%)
- Urination and defecation (1%)

Question 25

What are the body’s adaptive responses to cold environments?

Answer 25

3 to pass:
- Muscular: shivering, increased voluntary activity, curling up
- Vascular: vasoconstriction
- Increased noradrenaline and adrenaline secretion
- Hunger
- Horripilation

Question 26

How does the body produce heat?

Answer 26

Basal metabolic processes*
Food intake

• needed to pass

Question 27

What part of the brain controls the reflex responses activated by cold?

Answer 27

Posterior hypothalamus

Question 28

Where is thirst regulated?

Answer 28

Hypothalamus in the diencephalon

Question 29

What factors increase third?

Answer 29

1. Increased osmotic pressure in plasma*
   - Sensed by osmoreceptors in the anterior hypothalamus
2. Decreased ECF volume*
   - E.g. in haemorrhage
   - Sensed by baroreceptors in heart and blood vessels to increase thirst
   - Increased in renin -> AT II -> acts on diencephalon neurons to increase thirst
3. Psychological
   - E.g. acute psychosis
4. Others:
   - Increased liquids during eating (prandial drinking)
   - Other poorly understood mechanisms such as increased osmolality as food is absorbed, and GI hormones acting on the hypothalamus

Question 30

In what situations may thirst sensation be blunted?

Answer 30

Hypothalamic disease
Direct damage to the diencephalon
Altered mental state*
Psychosis
Lesion of anterior communicating artery (supplies the hypothalamus)
Diet high in protein (products of protein metabolism cause water diuresis)

• needed to pass + one other

Question 31

Describe the neural connections of the visual pathway

Answer 31

Retina* -> optic nerve* -> optic chiasm* -> optic tract* -> lateral geniculate body (hypothalamus) -> geniculocalcarine tract -> primary visual cortex (occipital lobe)*

At the optic chiasm, nasal fibres decussate to the contralateral side*

Other connections:
- Pupillary reflexes and eye movements: optic tract (via superior colliculus) to pretectal midbrain, then to Edinger-Westphal nuclei in the oculomotor nerve
- Refined eye movements (vergence, near-point response): frontal cortex
- Endocrine and circadian responses to day/night cycle: retinal ganglion cells to suprachiasmatic nucleus in the hypothalamus

• needed to pass

Question 32

Why is the fovea important for visual acuity?

Answer 32

Fovea is the centre of the macula, a thinned out rod-free portion of the retina where cones are densely packed* and each synapses on a single bipolar cell which in turn synapses on a single ganglion cell, providing a direct pathway to the brain
It is the point where visual acuity is the greatest*

• one of these + one other to pass

Question 33

What ocular factors influence visual acuity?

Answer 33

1. Optical factors:
   - State of the image-forming mechanisms (e.g. cataracts, keratitis, astigmatism, myopia, hyperopia)
2. Retinal factors:
   - E.g. state of cones (retinopathies, optic neuritis)
3. Stimulus factors:
   - E.g. illumination, brightness of stimulus, contrast between stimulus and background, length of time exposed to stimulus