Physiology Lecture 9: Understanding Autonomic Dysreflexia and the Sympathetic Nervous System

Sympathetic Nervous System (SNS)

The component of the autonomic nervous system that responds to stressful situations by initiating the fight-or-flight response. More active during activities and expends energy.

Parasympathetic Nervous System

The division of the autonomic nervous system that calms the body. It is more active at rest and conserves the body's energy. Mainly involved in digesting a meal.

Common Misconception of SNS and PSNS

That excitation of SNS only produces excitatory response and same thing for PSNS. This is NOT correct. Either system can produce an excitatory or inhibitory response, it depends on the organ it is functioning on.

Common Implication of SNS and PSNS

The blockade of the effects of one nervous system can appear similar to the excitation of the other. For example, stimulation of the parasympathetic nervous system decreases heart rate; similarly, blockade of the sympathetic nervous system can reduce heart rate.

Homeostasis

Autonomic NS controls the internal state of the body, thus controlling homeostasis.

Characteristics of ANS

1. 2 neurons involved

2. innervates smooth and cardiac muscle, glands, and GI neurons

3. NT at the effector organ can be ACh and/or NE

4. Receptor at effector organ can be muscarinic or adrenergic

5. The response of the effector organ can be either inhibitory or excitatory.

(all of this occurs at the post-ganglia site)

SNS vs. PSNS differences

1) Areas of CNS from which the preganglionic neurons emerge 2) Location of ganglia

3) Type of neurotransmitter released from the postganglionic neurons

4) The internal organs they innervate

SNS/PSNS: Location of cell bodies of pre-ganglionic neurons

SNS: Intermediolateral nuclei (IML) of spinal cord segments (T1-L3)

PSNS: Brain stem, nuclei of cranial nerves (3, 7, 9, and 10= VAGUS) and spinal cord segments 2-4

SNS/PSNS: Location of ganglia

SNS: para/prevertebral

PSNS: in walls of internal effector organs

para: runs along the spinal cord

pre: in front of the spinal cord

SNS/PSNS: NT secreted by PREganglia

SNS: ACh

PSNS: ACh

SNS/PSNS: Receptors activated by PRE-ganglionic neurons

SNS: nAChR type 2

PSNS: nAChR type 2

SNS/PSNS: NT secreted by POST-ganglionic neurons/cells

SNS: NE (most), 20% NE and 80% Epi in the adrenal medulla, ACh (single innervation)

PSNS: ACh

SNS/PSNS: Receptors activated by POST-ganglionic neurons

SNS: alpha and beta (for NE and Epi)

mAChRs (for ACh; muscarinic)

PSNS: mAChRs (for ACh; muscarinic)

Single Innervation

Occurs in sweat glands, arrector pili muscles, many blood vessels, and the adrenal medulla (chromaffin cells).

Only SNS innervates.

Epi and NE Characteristics

Epinephrine and Norepinephrine are secreted by chromaffin cells in the adrenal medulla that is only innervated by the SNS.

NE and Epi are very similar NT's. They act on the same receptors.

Epi has more effect on heart and NE has more effect on blood vessels.

Cholinergic Transmitter

ACh, activation of ACh receptors always causes cell depolarization

Cholinergic Receptors

1. Nicotinic (N1 nAChR= skeletal and N2 nAChR= on ALL postganglionic neurons and chromaffin cells)

2. Muscarinic (mAChR) (M1, M3 and M5 are excitatory. M2 and M4 are inhibitory)

Cholinergic NT and Receptor Response

1. ACh stimulation of N1 nAChR at neuromuscular junction leads to excitation and contraction of skeletal muscle

2. ACh stimulation of N2 nAChR at autonomic ganglia excite SNS and PSNS post-ganglia neurons (does not discriminate SNS/PSNS)

3. ACh stimulation of mAChR at effector organs can inhibit or excite the organ depending on the organ and its type of M receptor.

Cholinergic Receptor Agonists

1. N1 nAChR= ACh and nicotine

2. N2 nAChR= ACh and nicotine

3. mAChR= ACh and muscarine

Cholinergic Receptor Antagonists

1. N1 nAChR= Curare (muscle relaxant)

2. N2 nAChR= trimethaphan (ganglia blocker) (no discrimination)

3. mAChR= atropine (block inhibition or excitation of organ)

Adrenergic Neurotransmitters

1. Norepinephrine: primary NT for SNS post-ganglia neurons

2. Epinephrine: released only from adrenal medulla. Most NE is converted to Epi in chromaffin cells.

Adrenergic Receptors

1. Alpha 1 and 2

2. Beta 1, 2 and 3

Alpha Receptors

Stimulated by NE and/or Epi. Produce excitatory effects everywhere except in the GI tract, where they produce inhibitory.

1. Alpha 1: primary receptor on effector organs and tissues

2. Alpha 2: produces similar effects to A1 and also on organs and tissues.

3. some presynaptic alpha2 receptors that provide presynaptic inhibition

Alpha Agonists and Antagonists

Alpha 1 agonist: phenylephrine, NE, and Epi

Alpha 2 agonist: NE and Epi

Alpha 1 and 2 antagonist: Phentolamine

Beta Receptors

Stimulated by NE and/or Epi. They produce inhibitory effects everywhere except the heart, where they produce excitatory effects.

Beta 1: found primarily in the heart and stimulation of these excites the heart

Beta 2: located in most organs, inhibitory effect

Beta 3: only in fat cells, excited by circulating epinephrine. Meditate lipolysis

Beta Agonists and Antagonists

Beta 1 and 2 Agonist: NE, Epi, and Isoproterenol

Beta 3 Agonist: Epi and Isoproterenol

Beta 1-3 Antagonist: Propranolol

Tonic Activity

-Most internal organs receive dual innervation (from both the SNS and PSNS)

-Both systems are tonically active - they provide tonic (i.e., non-stop) excitation or inhibition to internal organs

-SNS and PSNS change the autonomic functions in different directions

Functional Synergism

-implies that when the activity of one system increases, the activity of the other system decreases. SNS and PSNS work together to produce an effect

-also implies that stimulation of one system appears as a blockade of the other system

Regulation of Blood Pressure

Blood vessels only have single innervation from SNS and do not exhibit functional synergism. Can regulate via:

1. Change in blood vessel diameter

2. Distribution and effects of activation of different receptors

3. Baroreceptor Reflex

1. Change in Blood Pressure Diameter

Main mechanism. SNS provides a "vasomotor tone" that is always "on"

An increase in the frequency of APs causes vasoconstriction and an increase in blood pressure

A decrease in the frequency of APs causes vasodilation (relaxation) and a decrease in blood pressure

2. Activation of Different Receptors

-Alpha 1 receptors in blood vessels of the skin induce vasoconstriction (excite, less blood)

-Beta 2 receptors in blood vessels of skeletal and cardiac muscles induce vasodilation (inhibit, more blood)

3. Baroreceptor Reflex

Used to control short term changes in blood pressure. If, for example, blood pressure decreases for some reason, the result of the baroreflex will be to increase blood pressure back to the normal level.

Baroreceptor Reflex Mechanism

1. Baroreceptors located in carotid and aorta

2. Increase in BP causes wall of carotid and aorta to stretch. Stretching induces APs to fire at a higher rate, coincides with increased baroreceptor activity.

3. AP travels along vagus and glossopharyngeal nerves to the nucleus of the tractus solitarius (NTS) in brainstem

4. NTS activates parasympathetic system in response to increased baroreceptor activity and inhibits sympathetic system. (Returns body to resting BP)

5. Since PSNS and SNS have opposite effects on BP, they work together to reduce it.

Hypertension

Increased blood pressure caused by an increase in the tonic or basal level of sympathetic tone to the heart and blood vessels (many different causes)

Pheochromocytoma

Increased blood pressure caused by tumor of the chromaffin cells in the adrenal gland; this is associated with massive secretion of NE and Epi

Postural (orthostatic) hypotension

Characterized by a drop in arterial pressure by 30 mmHg upon standing; associated with dizziness; occurs due to inadequate reflex control of blood pressure by the SNS.

Horner Syndrome

Characterized by miosis (excessive constriction of the pupil), ptosis (drooping of eyelid) and anhidrosis (loss of sweating); this results from loss of sympathetic innervation to the head

Autonomic diabetic neuropathy

This disease can occur in diabetics due to degeneration of small nerve fibers; disfunction of any or all parts of the ANS may occur leading to a wide variety of problems

Autonomic dysreflexia (aka sympathetic hyperreflexia)

Occurs with a spinal cord lesion at the T6 level or above; characterized by very high blood pressure that is triggered by internal stimuli; the lesion prevents the reduction of the increased blood pressure that normally is provided by the decrease in sympathetic activity