Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 13 Physiology of the Peripheral Nervous System

2Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Physiology of the Peripheral Nervous System  Divisions of the nervous system  Overview of autonomic nervous system functions  Basic mechanisms by which the autonomic nervous system regulates physiologic processes  Anatomic considerations  Introduction to neurotransmitters of the peripheral nervous system

3Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Physiology of the Peripheral Nervous System  Introduction to receptors of the peripheral nervous system  Exploring the concept of receptor subtypes  Locations of receptor subtypes  Functions of cholinergic and adrenergic receptor subtypes  Receptor specificity of adrenergic neurotransmitters  Neurotransmitter life cycles

4Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Divisions of the Nervous System  Central nervous system  Brain and spinal cord  Peripheral nervous system  Somatic motor  Autonomic (ANS) Parasympathetic Parasympathetic Sympathetic Sympathetic

5Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Overview of Autonomic Nervous System Functions  Three principal functions  Regulate the heart  Regulate secretory glands (salivary, gastric, sweat, and bronchial)  Regulate smooth muscles (bronchi, blood vessels, urogenital system, and GI tract)

6Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Parasympathetic Nervous System  Seven regulatory functions  Slowing the heart rate  Increasing gastric secretions  Emptying the bladder  Emptying the bowel  Focusing the eye for near vision  Constricting the pupil  Contracting bronchial smooth muscle

7Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Parasympathetic Nervous System  Parasympathetic nervous system (PNS) drugs  Digestion of food  Excretion of waste  Control of vision  Conservation of energy

8Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Sympathetic Nervous System Functions  Three main functions 1.Regulation of cardiovascular system Maintaining blood flow to the brain Maintaining blood flow to the brain Redistributing blood Redistributing blood Compensating for loss of blood Compensating for loss of blood

9Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Sympathetic Nervous System Functions  Three main functions (cont’d): 2.Regulation of body temperature Regulates blood flow to the skin Regulates blood flow to the skin Promotes secretion of sweat Promotes secretion of sweat Induces piloerection (erection of hair) Induces piloerection (erection of hair)

10Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Sympathetic Nervous System Functions  Three main functions (cont’d): 3. Implementation of “fight-or-flight” reaction Increasing heart rate and blood pressure Increasing heart rate and blood pressure Shunting blood away from the skin and viscera Shunting blood away from the skin and viscera Dilating the bronchi Dilating the bronchi Dilating the pupils Dilating the pupils Mobilizing stored energy Mobilizing stored energy

11Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Homeostatic Objectives of SNS  Maintenance of blood flow to the brain  Redistribution of blood flow during exercise  Compensation for loss of blood, primarily by causing vasoconstriction SNS = sympathetic nervous system.

12Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. SNS Body Temperature Regulation  Regulates blood flow to the skin  Dilating surface vessels: accelerates heat loss  Constricting cutaneous vessels: conserves heat  Promotes secretion of sweat glands: helps the body cool  Induces piloerection: promotes heat conservation

13Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Fight-or-Flight Response  Increasing heart rate and blood pressure  Shunting blood away from the skin/viscera and into skeletal muscle  Dilating the bronchi to improve oxygenation  Dilating the pupils  Mobilizing stored energy, thereby providing glucose for the brain and fatty acids for the muscles

14Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Sympathomimetic Drugs  Primarily used for effects on the  Heart and blood vessels Hypertension, heart failure, angina pectoris Hypertension, heart failure, angina pectoris  Lungs Primarily asthma Primarily asthma

15Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Basic Mechanisms by Which ANS Regulates Physiologic Processes  Patterns of innervation and control  Feedback regulation  Autonomic tone ANS = autonomic nervous system.

16Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Basic Mechanisms by Which ANS Regulates Physiologic Processes  Patterns of innervation and control  Dual innervation opposed: heart rate  Dual innervation complementary: erection and ejaculation  Only one division: blood vessels

17Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Fig Opposing effects of parasympathetic and sympathetic nerves.

18Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Basic Mechanisms by Which ANS Regulates Physiologic Processes  Feedback regulation  Baroreceptor reflex and blood pressure  Feedback loop  Sensor, effector neurons

19Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Fig Feedback loop of the autonomic nervous system.

20Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Basic Mechanisms by Which ANS Regulates Physiologic Processes  Autonomic tone  Only one division provides basal control to organ. Most organs: predominant tone is PNS Most organs: predominant tone is PNS Vascular system: predominant tone is SNS Vascular system: predominant tone is SNS

21Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Anatomic Considerations  Parasympathetic nervous system  Sympathetic nervous system  Somatic motor system

22Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Fig The basic anatomy of the parasympathetic and sympathetic nervous systems and the somatic motor system.

23Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Sympathetic Nervous System  Neurons  Preganglionic neurons  Postganglionic neurons  Medulla of the adrenal gland  Functional equivalent of the postganglionic SNS neuron

24Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Sympathetic Nervous System   Two general sites of action   Synapses: preganglionic/postganglionic   Junction: postganglionic neurons/effector organs

25Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Neurotransmitters of the Peripheral Nervous System Employed at most junctions of the peripheral nervous system Acetylcholine Released by most postganglionic neurons Norepinephrine Released by the adrenal medulla Epinephrine

26Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Fig Transmitters employed at specific junctions of the peripheral nervous system.

27Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Receptors of the Peripheral Nervous System Two basic categories of receptors Cholinergic receptors Mediated by acetylcholine Adrenergic receptors Mediated by epinephrine and norepinephrine

28Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Receptors of the Peripheral Nervous System Subtypes of cholinergic and adrenergic receptors Subtypes of cholinergic receptors Nicotinic N Nicotinic M Muscarinic Subtypes of adrenergic receptors Alpha 1 Alpha 2 Beta 1 Beta 2 Dopamine

29Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Fig Drug structure and receptor selectivity.

30Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Exploring the Concept of Receptor Subtypes  What do we mean by the term receptor subtype?  How do we know that receptor subtypes exist?  How can drugs be more selective than natural neurotransmitters at receptor subtypes?  Why do receptor subtypes exist?  Do receptor subtypes matter to us? You bet!

31Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Locations of Receptor Subtypes  Knowledge of the sites at which specific receptor subtypes are located will help predict which organs a drug will affect.

32Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Classification of Cholinergic and Adrenergic Receptors Cholinergic Receptors Adrenergic Receptors Mediated by acetylcholine Mediated by epinephrine and norepinephrine

33Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Functions of Cholinergic and Adrenergic Receptor Subtypes  Functions of cholinergic receptor subtypes  Activation of nicotinic N (neuronal) receptors  Activation of nicotinic M (muscle) receptors  Activation of muscarinic receptors

34Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Fig Locations of cholinergic and adrenergic receptor subtypes.

35Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Functions of Adrenergic Receptor Subtypes  Alpha 1  Vasoconstriction  Ejaculation  Contraction of bladder neck and prostate  Alpha 2  Located in presynaptic junction  Minimal clinical significance

36Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Functions of Adrenergic Receptor Subtypes  Beta 1  Heart  Increases Heart rate Heart rate Force of contraction Force of contraction Velocity of conduction in atrioventricular (AV) node Velocity of conduction in atrioventricular (AV) node  Kidney  Renin release

37Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Functions of Adrenergic Receptor Subtypes  Beta 2  Bronchial dilation  Relaxation of uterine muscle  Vasodilation  Glycogenolysis  Dopamine  Dilates renal blood vessels

38Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Receptor Specificity of the Adrenergic Neurotransmitters  Epinephrine can activate all alpha and beta receptors, but not dopamine receptors.  Norepinephrine can activate alpha 1, apha 2, and beta 1 receptors, but not beta 2 or dopamine receptors.  Dopamine can activate alpha 1, beta 1, and dopamine receptors. Note: Dopamine is the only neurotransmitter capable of activating dopamine receptors.

39Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Neurotransmitter Life Cycles  Many drugs produce their effects by interfering with specific life cycles.  Life cycle of acetylcholine  Life cycle of norepinephrine  Life cycle of epinephrine

40Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 3 Fig Life cycle of acetylcholine. Note that transmission is terminated by enzymatic degradation of ACh and not by uptake of intact ACh back into the nerve terminal. (Acetyl CoA = acetylcoenzyme A, ACh = acetylcholine, AChE = acetylcholinesterase.)

41Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Fig Life cycle of norepinephrine. Note that transmission is terminated by reuptake of NE into the nerve terminal and not by enzymatic degradation. Note also the structural similarity between epinephrine and norepinephrine. (DA = dopamine, MAO = monoamine oxidase, NE = norepinephrine.)