Physio Autonomic NS (6)

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Physio Autonomic NS (6)
2014-01-22 19:52:29
MBS Physiology
Exam 1
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  1. Autonomic Nervous System (ANS)
    • an involuntary system that regulates all the “vegetative” functions of the body
    • has afferent input from Visceral afferents (eg. arterial BP, visceral pain), Somatic afferents (eg. surface pressure & pain), and Special senses (eg. visual, auditory)
  2. What are the 3 divisions of the motor portion of the ANS?
    • 1. parasympathetic
    • 2. sympathetic
    • 3. enteric
  3. Autonomic Reflexes
    • unconscious or automatic responses that occur in specific patterns in response to specified sensory signals
    • such reflexes can be demonstrated at the level of the spine, medulla oblongata, hypothalamus, & high centers like the thalamus or cortex
  4. ANS Spinal Reflexes
    sweating & changes in cardiac & vascular function in response to pain or temperature stimulation
  5. ANS Medulla Oblongata Reflexes
    • where integration for blood pressure control occurs
    • sensory input comes from stretch receptors (baroreceptors) in the walls of the aorta & carotid arteries
  6. ANS Hypothalamus Reflexes
    • the principal center for integration of the entire ANS
    • contains nuclei integrating parasympathetic & sympathetic function
  7. ANS Higher Centers Reflexes
    • serve as a place to integrate special sensory input
    • eg. thalamus and cortex
    • PNS & SNS signal integration is mediated by CNS
  8. SNS Activity Increases During:
    • Stress
    • Anxiety
    • Physical Activity
    • Fear
  9. PNS Activity Increases During
    • Sedentary Activity - things that happen when we're at rest
    • Digestion/Eating
    • “Vegging”
  10. What happens when output increases in one division (SNS or PNS) of the peripheral ANS?
    when output INCREASES in one division, it DECREASES in the other (don't get both types of stimulation to one organ at the same time)
  11. Somatic Motor Neurons
    • a neuron with a cell body located in the CNS innervates skeletal muscle
    • upon activation neurons release ACh which act on nicotinic (N1) receptors on skeletal muscle cells at the NMJ
  12. Pre-ganglionic Neuron of the PNS
    • has a cell body in the CNS, whose axon exits with a cranial or sacral nerve
    • said neurons' axons exit the spinal chord & near to the effector organ in question, synapse w/ a postganglionic neuron in a parasympathetic ganglion
    • preganglionic >> postganglionic (length-wise)
  13. Post-ganglionic Neuron of the PNS
    consist of short axons that innervate target organ cells
  14. Parasympathetic Neurons
    • long pre-ganglionic nerves originate in the CNS & synapse with short post-ganglionic nerves close to effector organs (smooth/cardiac muscle or glands)
    • ACh is released at both ganglionic & effector organ synapses
    • PNS ganglionic receptors: nicotinic (N2)
    • effector organ receptors: muscarinic*
  15. Which NT & which receptor function at parasympathetic nervous system ganglia?
    • NT = acetylcholine (ACh)
    • receptor = nicotinic
  16. What is the eventual effector receptor types, NT that works at said receptor, and the organ systems innervated in the post-ganglionic parasympathetic nervous system?
    acetycholine activates muscarinic receptors on cardiac muscle, smooth muscle, & glands
  17. Pre-ganglionic Neuron of the SNS
    • has its cell body in Interomediolateral columns of the spinal cord at levels C8 → L3
    • its axon exit in the anterior (ventral) nerve roots & synapse with post-ganglionic neurons in the sympathetic ganglia of
    • 1. the sympathetic chain
    • 2. collateral ganglia (eg. celiac ganglion)
    • 3. terminal ganglia (near target organs, eg. bladder)
  18. Post-ganglionic Neuron of the SNS
    • has its cell body in a Paravertebral sympathetic chain ganglia or Collateral ganglia
    • has a long axon that extends to target tissues
  19. Sympathetic Neurons
    • short pre-ganglionic nerves originate in the CNS & synapse near the spinal chord w/ long post-ganglionic nerves
    • ACh is released at all ganglionic synapses of the SNS
    • NE is released at target organ synapses of the SNS
  20. Which NT & which receptor function at sympathetic nervous system ganglia?
    • NT = acetylcholine (ACh)
    • receptor = nicotinic (N2)
  21. What are the eventual effector receptor types, NTs that work at said receptors, and the organ systems innervated in the post-ganglionic sympathetic nervous system?
    • 1. norepinephrine → α or β receptors on cardiac muscle, smooth muscle, & glands
    • receptors are coupled to G-proteins; function via a 2nd messenger system
    • *NE is the main NT that innervates effector organs
  22. How does the sympathetic nervous system stimulate the adrenal medulla?
    • directly - there is no intermediate ganglion (sort of acts like a POST-ganglionic fiber)
    • ACh acts on nicotinic (N2) receptors on the adrenal medulla
    • the adrenal medulla in turn releases norepinephrine or epinephrine into circulation
  23. Sympathetic Chain (Trunk)
    • a paired bundle of nerve fibers that run from the base of the skull to the coccyx
    • where many of the ganglion of the the SNS are located
    • it can be found just outside the spinal chord
  24. Collateral Ganglia
    • nerves that travel down the spinal chord but bypass the sympathetic chain & synapse with ganglia outside of it (farther away from the spinal chord)
    • includes celiac, superior, & inferior mesenteric ganglia
  25. Where do the outputs from the PNS come from?
    • cranial and sacral parts of the CNS (spinal chord)
    • why it's called cranio-sacral

  26. Where do the outputs of the SNS come from?
    • sympathetic output is thoraco-lumbar (T1 → L3/4)
    • while they originate in this middle-spinal region, SNS nerve axons can spread out through the spinal chord to reach all visceral organs of the body

  27. How do muscarinic receptors of the post-ganglionic parasympathetic system communicate to visceral target cells?
    • upon ACh stimulation, the PNS muscarinic receptors interact w/ heterotrimeric G-PROTEINS to bring about 1 of 3 responses:
    • 1. hydrolysis of phosphoinositide → increasing Ca2+ → activating protein kinase C
    • 2. inhibition of adenylyl cyclase → decreasing cAMP levels
    • 3. modulating K+ channels (via G-Protein βγ complex)
  28. How does the timing of muscarinic (PNS) responses compare to nicotinic (most SNS) responses?
    b/c muscarinic responses are mediated by second messenger systems, in contrast with nicotinic responses, they tend to be SLOW & prolonged
  29. N1 Receptor
    • nicotinic receptor agonized by
    • 1. ACh
    • 2. decamethonium

    • & antagonized by
    • 1. D-tubocurarine
    • 2. α-Bungarotoxin

    is located on muscle cells at the NMJ; functions in the somatic motor system

    are directly coupled to ion channels; DON'T function via 2nd messenger
  30. N2 Receptor
    • nicotinic receptor agonized by
    • 1. ACh
    • 2. Tetramethylammonium

    • & antagonized by
    • 1. hexamethonium

    are located in ANS ganglia (SNS & PNS) & on adrenal medulla cells

    are directly coupled to ion channels; DON'T function via 2nd messenger
  31. Muscarinic Receptors M1, M3, & M5
    • are all stimulated by ACh & muscarine but blocked by atropine & pirenzepine
    • functions by activating the 2nd messengers IP3 & diacylglycerol
  32. Muscarinic Receptors M2 & M4
    • are both stimulated by ACh & muscarine but blocked by atropine & M2 is blocked by methoctramine
    • functions by decreasing the level of the 2nd messenger cAMP
  33. Adrenergic Receptors
    • α1 & α2 preferentially bind to NE > EPI → agonism
    • β1, β2, & β3 preferentially bind to EPI > NE → agonism
    • all work via 2nd messengers
    • α1: IP3 & diacylglycerol
    • α2: ↓ cAMP
    • β1: ↑ cAMP
    • β2: ↑ cAMP
    • β3: ↑ cAMP
  34. α1 Adrenergic Receptors
    • found most abundantly in blood vessels (*especially arterioles)
    • stimulation usually CONSTRICTS vessels via Ca2+ mobilization caused by 2nd messengers IP3 & diacylglycerol
    • α1 activation results in elevated BP [b/c of BV constriction]
  35. α2 Adrenergic Receptors
    • located primarily on the surface of PRE-synaptic neurons in the brain
    • when stimulated they SUPPRESS the release of norepinephrine from pre-synaptic terminals by inhibiting adenylate cyclase
    • *are sometimes referred to as auto-inhibitory receptors
    • [alpha-2 will auto-inhibit YOU]
  36. β1 Adrenergic Receptors
    • primarily located in the heart
    • when stimulated they INCREASE heart rate & contractility by ↑ cAMP & activating adenylate cyclase
  37. β2 Adrenergic Receptors
    • located primarily in the lungs, specifically bronchial smooth muscle
    • when stimulated they cause bronchodilation by ↑ cAMP & activating adenylate cyclase
  38. β3 Adrenergic Receptors
    located on adipose cells where they mediate lipolysis (the breakdown of lipids; involves hydrolysis of TAGs into glycerol & free FAs)
  39. How do the actions of the SNS & the PNS work in opposition to each other?
    • 1. by having opposing smooth muscles innervated separately - 1 by the PNS, the other by the SNS (eg. iris)
    • 2. by having the same cells innervated by both PNS & SNS neurons, expressing receptors for both ACh & NE (eg. heart's sino-atrial node (pacemaker))
  40. Pupil
    • dilation occurs via sympathetic stimulation which contracts the Radial smooth muscle by activating α1 receptors
    • constriction occurs via parasympathetic stimulation which contracts the Sphincter smooth muscle by activating muscarinic receptors
    • SNS activates the dilating muscle (radial, organized like spokes of a wheel)
    • PNS activates the constricting muscle (sphincter, circular, runs around the iris)
  41. ANS & Sino-atrial Node
    • SNS stimulation of the Cardiac plexus speeds firing rate via β receptors
    • PNS stimulation of the Vagus nerve SLOWS firing rate via muscarinic receptors
    • heart has receptors for BOTH systems
  42. EPI Synthesis
    • Tyrosine
    • ↓ (+ OH)
    • Dopa
    • ↓ (- COOH)
    • Dopamine (+ OH)
    • ↓ (+ OH)
    • NE
    • ↓ (+CH3 via phenylethanolamine-N-methyltransferase)
    • EPI
    • *in the final step epinephrine is made from norepinephrine by the action of N-methyl transferase, an enzyme only found in adrenal medullary cells
  43. What enhances the activity of N-methyl transferase in adrenal medullary cells?
    • steroids from the adrenal cortex delivered via a small portal system to the medulla
    • means an increased synthesis of EPI from NE
  44. Exceptions to Aforementioned Rules
    • 1. although most receptors at ANS ganglia are N2 nicotinic, MUSCARINIC receptors may sometimes be found in ganglia (ACh can bind & activate both receptor types)
    • 2. there are non-cholinergic, non-adrenergic transmitters in the ANS (co-transmission)
  45. When would a biphasic response be seen in a post-ganglionic neuron?
    when at the ganglion it contains both N2 & Muscarinic receptors

    N2 stimulation by ACh results in fast post-ganglionic EPSPs (b/c they directly control ion channels)

    Muscarinic stimulation by ACh results in slow post-ganglionic EPSPs (b/c they are G-protein coupled)

    this applies to both SNS & PNS ganglia

  46. Co-transmission
    in many pre & post ganglionic neurons of the ANS, transmitters in addition to ACh & NE are expressed & participate in neurotransmission
  47. How is Norepinephrine inactivated?
    • 1. mainly by re-uptake into adrenergic nerve terminals via active transport
    • 2. the enzyme catechol-O-methyl transferase may inactivate NE (+ other catecholamines) by methylating an OH group; this enzyme is present NEAR the postsynaptic membranes of most target tissues
    • 3. by MAO (monoamine oxidase) INSIDE the neuron
  48. What might inhibit the NE re-uptake pump?
    local anesthetics (+ cocaine) have been shown to inhibit the re-uptake, thereby increasing the concentration of NE available to target cell receptors