Autonomic nervous system physiology Flashcards
How can the ANS be classified
AFFERENT (sensory afferents transmit information from visceral structures, chemical and mechanical data from chemoreceptors and baroreceptors)
EFFERENT (controls cardiac muscle, smooth muscle and glands): two antagonistic divisions.
- SNS
- PSNS
Which structures are not innervated by the parasympathetic nervous system
Although most organs are innervated by both sympathetic and parasympathetic nerves, some-including the:
- adrenal medulla,
- arrector pili muscles,
- sweat glands, and
- most blood vessels-receive ONLY sympathetic innervation.
Where are the cell bodies for the pre-ganglionic ANS neurons found?
Brain or spinal cord
What type of axons are in preganglionic ANS neurons
B type fibres (diameter 2 um) velocity 10 m/s
myelinated but slow conducting
How many postganglionic cells does 1 pre-ganglionic cell synapse with?
8 - 9 –> diffuse ANS effect
What type of axons are in postganglionic ANS neruons
C-fibres (diameter 1 um), velocity 1m/s
un-myelinated and slow
From which spinal roots do the SNS preganglionic fibers emerge?
Thoracolumbar: T1 to L2
Where are the pre-ganglionic cell bodies found?
Lateral horn (grey matter) of the spinal cord
Describe the three ways that pre-ganglionic SNS axons can terminate after leaving the spinal cord?
- Synapse in the paravertebral sympathetic chain = series of sympathetic ganglie found alongside the vertebral column from the base of the skull to the coccyx
- Some pass through the sympathetic chain to synapse on PERIPHERAL AUTONOMIC GANGLIA
- Caeliac ganglion
- Superior mesenteric ganglion
- Inferior mesenteric ganglia - Few preganglionic SNS neurons synapse directly on chromaffin cells in the medulla of the adrenal gland
Describe the outflow of the PSNS from the CNS
Craniosacral
Cranial nerves: 3,7,9,10
- cell bodies are in cranial nerve nuclei
Spinal nerve roots S2 - S4
- cell bodies are in the lateral horns of the sacral spinal cord
The conus medullaris is at L1
The SAH space and dural sheath (and hence subarachnoid space) end at S2. –> LP avoids damage to spinal cord.
Where are PSNS ganglia
Ganglia from the vagus and sacral efferents are usually diffusely located in the walls of the viscera they supply
Cranial nerves 3, 7, 9 that supply the head and neck synapse in four discrete intermediary ganglia
- Ciliary
- Sphenopalatine
- Submaxillary
- Otic
How does the thoracolumbar SNS supply the head and neck and the pelvis
Preganglionic fibres from the thoracolumbar region travel up (or down) the paravertebral chain into cervical or sacral sympathetic ganglia to synaps with their postganglionic neurons
Which somatic pain fibres travel with PSNS efferents
Pain fibres from the lungs and pelvis travel with PSNS efferents
Which somatic pain fibres travel with SNS efferents
Pain fibres from the heart and abdominal viscera
Why is cardiac pain often referred to the arm and neck
Pain from viscera is poorly localized and is often ‘referred’ to the corresponding somatic segment
What therapeutic outcomes can be achieved by blocking the sympathetic pathways?
- Treat SNS overactivity
- Sympathetically mediated pain
- Visceral pain
Suggest clinical uses for the following sympathetic blocks:
Thoracic sympathectomy
Lumbar sympathectomy
Coeliac plexus block
Thoracic sympathectomy
- Raynauds phenomenon or hyperhidrosis (sweaty palms)
Lumbar sympathectomy
- Rx pain associated with circulatory insufficiency of the lower limb or phantom limb pain
Coeliac plexus block
- Rx pain associated with upper GI malignancy or acute/chronic pancreatitis
Which SNS postganglionic fibres use Ach instead of NA as a neurotransmitter
Merocrine sweat glands
Skeletal muscle blood vessels
Summarize the general properties of muscarinic receptors
- M1 - M5
- G-protein linked
- Brain, Heart, Smooth muscle, glands
- Actions are mimicked by muscarine (amanita mushroom)
- Actions are blocked by atropine
Summarize the general properties of the nicotinic receptors
- Found in ANS ganglia, the neuromuscular junction and merocrine sweat glands
- Ligand-gated ion channel receptors
- Mimicked by nicotine
- UNAFFECTED BY ATROPINE
When reversing non-depolarizing neuromuscular blockade, what classes of agent are given and why? What are the potential side effects and describe the mechanism of this and how it is prevented
Achase inhibitor (neostigmine) –> increase Ach within synaptic cleft –> competes with binding of non-depolarizing neuromuscular blocker.
The desired effect is to increase the Ach in the synaptic cleft in skeletal muscle to regain muscle function. But Ach is also increased at Muscarinic receptors since Achase is inhibited here too.
A Muscarinic blocking agent (Atropine or glycopyrrolate) is administered to prevent these unwanted muscarinic effects.
How are alpha 1, Beta 1 and beta 2 receptors different from alpha 2 receptors
The former are all post-synaptic receptors whilst alpha 2 can either be a pre-synaptic or post-synaptic receptor
How does noradrenalin and adrenalin affinity for alpha and beta receptors differ
Adrenalin ha a higher affinity for beta receptors
Noradrenalin has a higher affinity for alpha receptors
Describe the G-protein linked mechanism for each type of adrenoreceptor and state how this brings about its function.
Beta
Linked to Gs protein: Ligand binding –> GDP converted to GTP on alpha subunit of the seven transmembrane protein. alpha-GTP detach and activate Adenyl cyclase –> converts ATP to cyclic AMP (cAMP) increased intracellular cAMP –> Contraction of cardiac muscle/Smooth muscle relaxation/glycogenolysis depending on location and B1 or B2.
alpha 2
Linked to Gi protein: inhibits the above process.
alpha 1
Linked to a Gq protein: Ligand binding –> GDP –> GTP: alpha subunit of G-protein bound to GTP detach –> activate Phospholipase C–> 1. activates IP3 (Inositol Triphosphate) –> mediates Ca2+ release and 2. activates Diacyl Glycerol (DAG) which activates protein kinases –> both 1. and 2. lead to smooth muscle contraction and glycogenolysis
What types of adrenergic receptors are in the heart
Beta 1
In arterioles and veins (Coronary, skeletal muscle ) what types of adrenergic receptors exist and what is the effect of their activation?
Beta 2 –> Dilatation
alpha 1 –> constriction
Where are alpha 2 receptors found, what are their effects at these locations and give examples of alpha 2 receptor agonists
The role of the alpha(2)-AR family has long been known to include:
- presynaptic inhibition of neurotransmitter release,
- diminished sympathetic efferent traffic,
- vasodilation (pre-synaptic) and vasoconstriction (post-synaptic).
Clonidine is an alpha 2 receptor agonist
Indications for clonidine: epidural infusion form in cancer pain not controlled by opioid analgesics and as an adjunct in anesthesia
Which adrenergic receptors in the lungs lead to bronchodilatation?
B2
Which adrenergic receptors in the lungs inhibit secretion from glands when stimulated
a1
Which adrenergic receptors in the GIT decrease motility of the intestine when stimulated
a1, a2, B2
Which adrenergic receptors in the intestine cause constriction of intestinal sphincters when stimulated
a1, B2
Which adrenergic receptors in the skin cause piloerection
a1
Which receptor in the skin causes SNS mediated sweating
Muscarinic !
What does atropine do to the pupil and why
M antagonist –> relaxation of the sphinter (PSNS) of the iris –> unopposed contraction of the radial muscle (SNS) –> mydriasis
What effect does adrenalin have on the eye?
a1 agonist –> contraction of the radial muscle of the iris –> mydriasis
What is the MOA of ephidrine
Combined a and B agonist (weak) plus stimulates endogenous noradrenalin release
What is the MOA of Phenylephrine
a1 agonist
What is the mechanism of action of clonidine and what are the clinical uses of this drug
a2 agonist in brain stem –> activates an inhibitory neuron –> decreases SNS outflow from CNS –> decreased SVR, Renal vasc. resistance, HR, BP
Epidural clonidine may produce pain relief at spinal pre-synaptic and postjunctional a2 adrenoreceptors
Clinical use:
- hypertension (not initial choice)
- ADHD (decreased distractibility prefrontal cortex)
- Epidural pain management
- Sedation ICU (transition from dexmedetomidine to clonidine)
What is the mechanism of action of isoprenaline
Stimulates beta1- and beta2-receptors resulting in relaxation of bronchial, GI, and uterine smooth muscle, increased heart rate and contractility, vasodilation of peripheral vasculature
Beta receptors relax everything except the heart
What is the mechanism of action of Phentolamine
a-blocker
What is the mechanism of action of propranolol
Nonselective beta-adrenergic blocker (class II antiarrhythmic); competitively blocks response to beta1- and beta2-adrenergic stimulation which results in decreases in heart rate, myocardial contractility, blood pressure, and myocardial oxygen demand. Nonselective beta-adrenergic blockers (propranolol, nadolol) reduce portal pressure by producing splanchnic vasoconstriction (beta2 effect) thereby reducing portal blood flow.
What is the mechanism of action of Metoprolol
Selective inhibitor of beta1-adrenergic receptors; competitively blocks beta1-receptors, with little or no effect on beta2-receptors
What is the MOA of Labetalol
Blocks alpha1-, beta1-, and beta2-adrenergic receptor sites; elevated renins are reduced.
The ratios of alpha- to beta-blockade differ depending on the route of administration estimated to be 1:3 (oral) and 1:7 (IV) (Goa 1989).
What is the mechanism of action of neostigmine
AChase inhibitor
What are the side effects of neostigmine
Salivation Nausea Gut spasms Bronchoconstriction Bronchorrhoea Bradycardia
What are the side effects of Atropine
Dry mouth and dry secretions Blurred vision and dilated pupils Tachycardia Pyrexia Confusion Bronchodilation
What are the three common undesirable side effects of propranolol?
- Cold hands and feet
- Wheeze
- Worsening of intermittent claudication
Side effects occur because propranolol is a non-selective beta blocker
How does general anaesthesia affect the SNS
Reduction in SNS tone, fall in BP and inhibition of autonomic reflexes.
Surgical stimulation during light anaesthesia may be associated with SNS responses such as tachycardia, Increased BP and sweating
What procedures in the operating theatre might elicit a vasovagal episode and how can this be treated
Laryngoscopy
Traction on the eye
Traction on the peritoneum
Cervical dilatation
What is the effect of spinal block for caesarian section on blood pressure? How can this be treated
Sympathetic block from T4 - L2 causes widespread vasodilation, decreased SVR and decreased BP.
Rx: Co-load with isotonic balanced fluid solution and administration of phenylephrine
Apart from the diffuse vasodilation associated with spinal anaesthesia due to SNS block from T4 - L2, what additional effect does HIGH SPINAL block have on the CVS?
More profound hypotension due to greater sympathetic block and bradycardia from loss of sympathetic supply to the heart (T1 - T4).
Is block to T10 adequate for caesarian section?
No block to T4 is require to block afferents from the visceral peritoneum
