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1. Chapter 94 Autonomic Nervous System PY10.5: Describe and discuss structure and functions of reticular activating system, autonomic nervous system (ANS).

2. LEARNING OBJECTIVES # Describe the organization of the autonomic nervous system # Explain the functions of sympathetic and parasympathetic nervous systems # Explain the physiology of stress

3. INTRODUCTION Autonomic nervous system (ANS) is that portion of nervous system, which is concerned with the visceral functions of the body i.e., the functions that occur without our conscious knowledge. Sympathetic and parasympathetic divisions of the ANS are the two major efferent pathways controlling target tissues other than skeletal muscle. It controls the functions of the involuntary organs of the body such as heart and blood vessels, secretory epithelia, glands and all visceral organs. So it is also known as involuntary nervous system or vegetative nervous system or visceral nervous system . Vegetative functions are those bodily processes directly concerned with maintenance of life. This includes nutritional, metabolic and endocrine functions including eating, sleeping, bowel and bladder activity, etc. John Newport Langley in 1898 divided ANS into two divisions, sympathetic and parasympathetic nervous system. Skeletal muscles receive only excitatory inputs through alpha motor neuron whereas; most of the visceral organs receive both inhibitory and excitatory synaptic inputs through the sympathetic and parasympathetic divisions of the ANS.

4. GENERAL ORGANIZATION OF ANS The ANS has three divisions: 1. Sympathetic nervous system , or thoracolumbar outflow , it is called so because it takes origin from first thoracic to second or third lumbar segments of spinal cord (T 1 –L 2 ) 2. Parasympathetic nervous system , also known as craniosacral outflow since it originates from 3rd, 7th, 9th and 10th cranial nerves and from the 2nd, 3rd and 4th sacral segments of spinal cord. 3. Enteric nervous system

5. The sympathetic and the parasympathetic systems can act independently of each other but generally they work synergistically to control visceral activity. Increased sympathetic discharge occurs in conditions of stress, anxiety, physical activity, fear or excitement while increased parasympathetic discharge occurs during sedentary activity such as eating or at rest. Autonomic nervous system functions are mainly based on autonomic or visceral reflexes, which consist of receptor, afferent limb, center , efferent limb and effector organ. In somatic nervous system, the efferent neuron, which is the alpha motor neuron in the anterior horn of spinal cord, directly innervates the effector organ, which is the skeletal muscle. Here there is only one efferent neuron. In contrast to this, the ANS innervates target tissue by a two synapse pathway. Axons of these neurons come out of the CNS to make synapse with the postganglionic neurons in the peripheral ganglia interposed between the CNS and the target cell. Axons of the postganglionic neurons supply their target cells. Receptors in the ANS are situated in the internal visceral organs called visceroceptors . They are baroreceptors, chemoreceptors, thermoreceptors, osmoreceptors and nociceptors which are sensitive to stretch of heart . II. Afferents: All internal organs are densely innervated by visceral afferents. Afferents from receptors mainly travel with parasympathetic fibers to the center (spinal cord or brain).

6. III. Center: Organization of ANS occurs at five different levels: 1. Spinal cord 2. Brain stem 3. Hypothalamus 4. Limbic system (amygdaloid complex) 5. Prefrontal cortex.

7. Spinal cord is the lowest level for the control of autonomic function. Here, simple reflexes such as micturition and defecation are integrated. Sympathetic fibers originate from T 1 to L 2 or 3 segments of spinal cord. The spinal component of parasympathetic nervous system originates from S 2 to S 4 segments of spinal cord. Brain stem contains the major nuclei of ANS. . The cranial outflow of parasympathetic nervous system originates from the cranial nerve nuclei (III, VII, IX and X) located in the brain stem . . Reticular formation in the brain stem is one of the highest centers of autonomic function where respiratory center, vasomotor center and cardiac centers are integrated. Sympathetic fibers originate from the vasomotor center in the medulla. . Pupillary reflexes such as light reflex and accommodation reflex are integrated in the Edinger– Westphal nucleus of midbrain. . Nucleus tractus solitarius (NTS) in the medulla mediate respiratory and cardiovascular responses to autonomic activation. Hypothalamus controls most of the endocrine glands and is also responsible for temperature regulation. The posterior and lateral portions of the hypothalamus control the sympathetic division of ANS. Stimulation of posterior hypothalamus can activate the vasomotor center of medulla strongly enough to increase arterial blood pressure to more than twice normal. Sherrington described hypothalamus as the head-ganglion of the sympathetic nervous system.

8. Limbic system along with hypothalamus controls the emotional behavior of the individual such as fear, rage, sexual behavior, etc. Prefrontal lobe is highly developed in man and is concerned with the intellectual behavior of man. Control of ANS by cerebral cortex occurs primarily during emotional stress. In extreme anxiety, cerebral cortex can stimulate hypothalamus, which in turn stimulates the vasomotor center in the medulla oblongata. This increases rate and force of heart beat and blood pressure. IV. Efferents : The autonomic fibers from higher centers located in the brain stem, hypothalamus, limbic system, and the prefrontal lobe of cerebral cortex cross the midline in the brainstem and form part of reticulospinal tract and end in the lateral horn cells of spinal cord or the parasympathetic cranial nerve nuclei. Autonomic efferents (motor neurons) are pre-ganglionic and postganglionic neurons. V. Autonomic effector organs are smooth muscles, cardiac muscle and glands.

9. FUNCTIONAL ANATOMY OF SYMPATHETIC NERVOUS SYSTEM Sympathetic fibers take origin from T 1 to L 2 or 3 segments of spinal cord. Axons of preganglionic neurons arise from their cell body, which are myelinated slow-conducting type B fibers . They pass out of the spinal cord through the ventral root along with the axons of alpha motor neurons of somatic nervous system. The sympathetic efferents separate from the somatic motor axons and enter the white rami communicantes and enter the ganglia of paravertebral sympathetic chain [sympathetic trunk] . Although the preganglionic sympathetic fibers emerge only from T 1 to L 2 segments, the paravertebral sympathetic chain of ganglia extends from the base of the skull to the tip of coccyx on either side. There are approximately 22 ganglia in a chain. The most rostral ganglion, the superior cervical ganglion is formed by the fusion of C1 to C4 and supplies the head and neck. The middle cervical ganglion is formed by the fusion of C5 and C6 and the inferior cervical ganglion by the fusion of C7 and C8. The inferior cervical ganglion is usually fused with the first thoracic ganglion to form the stellate ganglion.

10. Segmental Distribution of Sympathetic Fibers . T 1 and T 2 : Head and Neck (through superior, middle and inferior cervical ganglia) . T 3 to T 6 : Thorax (paravertebral ganglia) . T 7 to T 11 : Abdomen and pelvis [paravertebral ganglia, celiac plexus along the abdominal aorta and hypogastric plexus along the internal iliac artery] . T 12 to L 2 : Leg.

11. FUNCTIONAL ANATOMY OF PARASYMPATHETIC NERVOUS SYSTEM Parasympathetic efferents arise from 3rd, 7th, 9th and 10th cranial nerve nuclei and from 2nd, 3rd and 4th sacral segments of spinal cord. Thus, it has got two divisions, cranial and sacral divisions. The preganglionic parasympathetic neurons distributed along with the II, VII, IX and X cranial nerves originate in four groups of nuclei: (a) the Edinger–Westphal nucleus in the midbrain, (b) the superior salivatory nucleus in upper medulla, (c) the inferior salivatory nucleus and upper part of nucleus ambiguus in the medulla, (d) the nucleus ambiguus and dorsal motor nucleus of vagus in the medulla. . Parasympathetic preganglionic fibers travel in the oculomotor nerve (III) and synapse in the postganglionic neurons in the ciliary ganglion . . The preganglionic fibers from the superior salivatory nucleus pass through the facial nerve (VII) and synapse with the postganglionic neurons in the pterygopalatine ganglion . The postganglionic fibers supplies lacrimal and nasal glands. Another branch of facial nerve carries preganglionic fibers to the submandibular ganglion and the postganglionic fibers supply the submandibular and sublingual salivary glands.

12. . The preganglionic fibers from the inferior salivatory nucleus pass through the glossopharyngeal nerve (IX) and synapse in the postganglionic neurons in the otic ganglion . The postsynaptic neurons supply the parotid gland. . Preganglionic parasympathetic fibers of vagus (X) join the esophageal, pulmonary and cardiac plexus and travel to terminal ganglia located within their target organs.

13. The sacral parasympathetic preganglionic neurons are located in S 2 to S 4 segments of spinal cord in a part similar to that of preganglionic sympathetic neurons although they do not form a distinct intermediolateral column. Sacral preganglionic parasympathetic axons leave through the ventral roots and travel with the pelvic splanchnic nerves to their terminal ganglia in the visceral structures of lower abdomen and pelvis (descending colon, rectum, urinary bladder, and lower portions of uterus). It also supplies nerve signals to the external genitalia to cause erection. The parasympathetic preganglionic fibers are long and end in ganglia which are located near the organ or within the organ. The postganglionic fibers supply the concerned organ. So, the postganglionic fibers are short in contrast to the sympathetic fibers which have long postganglionic fibers

14. Sympathetic and Parasympathetic Tone Normally, the sympathetic and the parasympathetic systems are continually active, and the basal rates of activity are called sympathetic and parasympathetic tone respectively. The normal sympathetic tone to the systemic arterioles keeps them constricted to about one half their maximum diameters. The parasympathetic tone to the blood vessels is negligible. In times of need, the degree of sympathetic stimulation can be increased above normal, so that the vessels can be constricted more. Conversely, by decreasing the sympathetic stimulation below normal, the arterioles can be dilated. If the background sympathetic tone was not there, the sympathetic system could cause only vasoconstriction, never vasodilation. Parasympathetic tone is prominent in the heart and the gastrointestinal tract (exception is sphincters of GIT which has a resting sympathetic tone). When the vagal supply to the heart is cut, the heart rate may increase to about 160/ minute. When the parasympathetic discharge to the gut is cut, there will be decreased gastrointestinal motility (atony) and when there is increased parasympathetic stimulation the gastrointestinal activity increases.

15. TYPES OF TRANSMISSION IN THE AUTONOMIC NERVOUS SYSTEM Sympathetic and parasympathetic nerve endings release neurotransmitters, such as acetylcholine and norepinephrine (noradrenaline). Depending on the type of neurotransmitter, the fibers are classified into cholinergic and adrenergic fibers. In some areas, nitric oxide is the neurotransmitter where the fibers are termed non-adrenergic non-cholinergic fibers. The enteric nervous system, which is now considered as a third division of ANS release many amines, amino acids and active peptides as co-neurotransmitters along with acetyl choline or adrenaline, e.g. VIP with acetyl choline and neuropeptide Y with noradrenaline ( refer enteric nervous system). Cholinergic transmission is seen in: . Preganglionic sympathetic nerve endings . Preganglionic parasympathetic nerve endings . Postganglionic parasympathetic nerve endings . Postganglionic sympathetic nerve endings supplying skeletal muscle blood vessels and sweat gland (Cholinergic transmission also occurs in the neuromuscular junction in the somatic nervous system)

16. Adrenergic transmission is seen in: . Rest of the postganglionic neurons of sympathetic nervous system. . Adrenal medulla is considered as a specialized sympathetic ganglion (the chromaffin cells of adrenal medulla are considered as postganglionic sympathetic neurons that do not have axon. Adrenaline and noradrenaline released from these cells due to sympathetic stimulation enter the bloodstream and act as hormones) Cholinergic Transmission Cholinergic transmission is similar to transmission at the neuromuscular junction. The nerve endings end in the effector cells as varicosities which contain vesicles of acetylcholine. Acetyl choline is synthesized in the nerve endings and varicosities. When an action potential reaches the nerve ending the presynaptic membrane becomes permeable to Ca2+ and Ca2+ enter the nerve ending. This leads to the release of acetylcholine to the synaptic cleft by exocytosis. When the effect is over, acetylcholine is destroyed by acetylcholine esterase into choline and acetate. Choline is taken back into the nerve terminal.

17. Actions of Acetylcholine in the Postsynaptic Membrane There are two types of receptors in the postsynaptic membrane for acetyl choline, muscarinic and nicotinic receptors .

18. Muscarinic Receptors All postganglionic parasympathetic neurons act through muscarinic Ach receptors on the postsynaptic target cell. When stimulated, the action of these receptors resembles the action of muscarine which is a mushroom poison. Sites of Muscarinic Receptors a. Postsynaptic membrane of effector organs supplied by postganglionic parasympathetic nerve endings b. Postganglionic cholinergic sympathetic nerve endings Nicotinic Receptors Nicotinic receptors on stimulation produce effects similar to that of nicotine . Nicotine in small doses stimulates the autonomic ganglia. Nicotinic receptors (subtype N2) are present on the membrane of autonomic ganglia, i.e., at the synapses between preganglionic and postganglionic neurons of both sympathetic and parasympathetic system. The nicotinic receptor can be blocked by hexamethonium in the autonomic ganglia and by d-tubo curarine at the neuromuscular junction

19. Adrenergic Transmission The neurotransmitter involved in adrenergic transmission is norepinephrine (NE). It is synthesized in the axoplasm of the terminal nerve endings of adrenergic fibers and transported into the vesicle. In the adrenal medulla, 80% of norepinephrine is converted to epinephrine by the enzyme methyl transferase which is present only in the adrenal medulla. Once norepinephrine is released into the synaptic cleft, after its action there are three fates for norepinephrine: 1. Reuptake into the adrenergic nerve ending by active transport. 2. Diffusion into the surrounding body fluid and blood. 3. Destruction by enzymes such as monoamine oxidase (MAO) and catecholamine-O-methyl transferase (COMT).

20. Adrenergic Receptors The adrenergic receptors are a class of G protein-coupled receptors. There are two major types of adrenergic receptors, alpha receptors and beta receptors. Their distribution in different organs differs. They are again subdivided as shown below, because certain chemicals affect only certain receptors. Norepinephrine excites mainly alpha receptors but excites beta receptors to a lesser extent. Epinephrine excites both types of receptors approximately equally. Therefore, the relative effects of norepinephrine and epinephrine on different effector tissues are determined by the types of receptors in the tissues. . Combination of norepinephrine with α1 receptors produces increase in intracellular Ca2+, which in turn activates protein kinase and produce metabolic effects in the cells. . NE + α2 receptors inhibit the enzyme adenylyl cyclase and decrease cAMP. . NE + β1 or β2 receptors stimulate adenylyl cyclase and increase cAMP.

21. FUNCTIONS OF AUTONOMIC NERVOUS SYSTEM 1. Autonomic nervous system (ANS) controls the motor functions of smooth muscles, cardiac muscle and glands. 2. It maintains homeostasis. Almost all the organs are supplied by both sympathetic and parasympathetic nerves. Normally, the two systems act synergistically to meet the specific demands of any given situation. . Parasympathetic nervous system is effective in peaceful day-to-day life. It is also known as anabolic nervous system since it is concerned with conservative, restorative and vegetative aspects of day-to-day activities. . Sympathetic system becomes more active during emergency conditions and stressful situations. . Sympathetic stimulation increases blood glucose and free fatty acid levels for supplying more energy . Sympathetic nervous system is also known as catabolic nervous system .

22. Alarm or Stress Response of the Sympathetic Nervous System In times of stress as in fright, flight, fight, etc., large portions of sympathetic system become stimulated, producing mass sympathetic discharge. This result in widespread reaction throughout the body called the sympathetic alarm or stress response. The following reactions occur in times of stress: . Dilatation of pupil letting more light to enter the eye. . Increase in heart rate and arterial blood pressure helps in better perfusion of vital organs and muscles. . Constriction of cutaneous blood vessels and decreased blood flow to gastrointestinal tract and kidneys help to increase the blood flow to active muscles. . Decreased threshold in the neurons of reticular formation and thus increasing mental alertness by activating ascending reticular activating system (ARAS). . Increase in blood glucose and free fatty acid level, supplying more energy. There is also increased rate of cellular metabolism throughout the body. . Increased glycolysis in liver and muscle All the above reactions called the sympathetic stress response make the animal to decide whether to stand and fight or to run. This is also called fight or flight reaction .

23. DISORDERS OF AUTONOMIC NERVOUS SYSTEM . Following sympathectomy, the person will not be able to overcome stressful situations. . Horner’s syndrome is due to lesion of the cervical sympathetics . There will be ptosis (drooping of eyelids due to paralysis of elevator palpebrae superioris), pupillary constriction ( miosis ) due to paralysis of dilator pupillae muscle, flushing of face on the affected side and reduced sweating on the ipsilateral face and neck ( hypohidrosis ). . Hirschsprung’s disease is a condition where there is congenital absence of myenteric plexus in a part of large intestine. . Raynaud’s disease is due to defective peripheral vascular innervation. It is especially seen in young women. . Multiple system atrophy (MSA) is an adult onset, sporadic, rapidly progressive, multisystem neuro-degenerative fatal disease characterized by features of Parkinsonism (bradykinesia); cerebellar gait, ataxia, nystagmus; autonomic and urogenital dysfunction and corticospinal disorders (extensor plantar response with hyper- reflexia ) . . Haddad syndrome is a combination of congenital central hypoventilation syndrome (CCHS) and Hirschsprung’s disease. This condition is due to mutations in the PHOX2B gene which lead to loss of development of the neurons of the visceral control system. PHOX2B is considered as the master gene of the visceral control system.

24. GENERAL ADAPTATION SYNDROME (GAS) Stress Stress is primarily a physical response, the body’s way of responding to any kind of demand or threat. It is a change in the environment that is perceived as a challenge or difficult situation, threat or danger which has negative or positive effects. Factors in the environment that trigger stress response are called stressors . During stress, there is increased secretion of ACTH from the pituitary gland and blood cortisol level will be elevated normally. There is also increased secretion of adrenaline and noradrenaline to prepare the body for physical action, fight or flight reaction or stress response. Symptoms of stress include palpitation, fatigue, irritability, difficulty in concentrating, lack of sleep, hair loss (alopecia areata), abdominal pain typical of acid peptic disease, etc. Hans Selye in 1936 proposed an integrative model for the stress response known as general adaptation syndrome (GAS). GAS is a term used to describe the body’s short-term and long-term reactions to stress.

25. Intense pleasure or joy such as travel, job promotion, marriage, etc. can also cause stress which is referred to as eustress . Opposite of eustress is distress which has negative effects. GAS represents a three-stage reaction to stress. This syndrome is called general adaptation syndrome because it is produced by agents, which have a general effect upon large portions of the body. Selye noted a triad in subjects with chronic stress (1) enlargement of adrenal cortex, (2) atrophy of thymus and other lymphoid tissues, and (3) development of bleeding ulcers in the stomach and duodenum. The three stages of GAS are: 1. Alarm reaction 2. Stage of resistance 3. Stage of exhaustion.

26. Alarm Reaction Alarm reaction is the immediate reaction to a stressor. In this initial phase, humans exhibit fight or flight response, which prepares the body for physical activity. There will be a decrease in the functioning of the immune system, making the subject susceptible to illness. There is increase in muscle tone; increase in blood pressure due to vasoconstriction and tachycardia; hyperglycemia, increased secretion of ACTH and catecholamines, loss of appetite, weight loss, etc. Stage of Resistance or Stage of Adaptation If the stress continues, the body adapts to the stressors. Changes occur in the body to reduce the effect of the stressor. There is increased secretion of glucocorticoids. There is increase in the level of glucose, fatty acids and amino acids in blood due to the lipolytic, catabolic and anti-anabolic actions of glucocorticoids. There will be neutrophilia, polycythemia, lymphocytopenia and eosinopenia. Stage of Exhaustion This stage occurs when the stress has continued for some. Although the body (in the second stage) tries to adapt to the demands of the environment initially, the body cannot maintain it indefinitely and so its resources get gradually depleted.

27. Treatment and Prevention Treatment includes avoiding stressors, changing one’s reaction to the stressors or relieving stress after the reaction to stress. Listening to music, aromatherapy, exercising, relaxation techniques, acceptance of a stressful situation etc., may relieve stress after it has occurred. A healthy life style is very important such as a balanced diet, enough rest and sleep, regular exercise, improvement of social skills, avoiding smoking and drinking, strengthening relationships, etc. Applied Aspects The concept of general adaptation syndrome (GAS) has important application in sports training. The purpose of training is to make the body adapt to the sport-specific stressors. Training should strengthen the physiological system.

28. MULTIPLE CHOICE QUESTIONS 1. True regarding ANS is: a. Higher center of integration in the medulla oblongata b. Conduction in autonomic fibers is same as in somatic motor fibers c. Preganglionic parasympathetic fibers are more lengthy d. Ratio of preganglionic and postganglionic fiber is 20:1 2. All are effects of sympathetic stimulation, except : a. Increased conduction velocity b. Increased heart rate c. Increased refractory period d. Increased contractility of heart 3. During flight and fight reaction, which of the following is responsible for increase in local blood flow? a. Sympathetic system mediated cholinergic release b. Local hormones c. Parasympathetic cholinergic discharge d. Endocrine factors only