4-autonomic-nervous-system-2.pdf

# Introduction to the autonomic nervous system The autonomic nervous system (ANS) is a vital component of the peripheral nervous system that regulates involuntary bodily functions [2](#page=2). ## 1. Introduction to the autonomic nervous system The autonomic nervous system (ANS) is part of the peripheral nervous system (PNS) and is responsible for the involuntary regulation of body functions. This contrasts with the somatic system, also part of the PNS, which operates voluntarily. The central nervous system (CNS) comprises the brain and spinal cord, while all structures connecting to or from the CNS are part of the PNS [2](#page=2). ### 1.1 Anatomy of the ANS ANS neurons carry information from the central nervous system to effector organs, functioning as efferent neurons. The ANS is characterized by two distinct rows of neurons: preganglionic and postganglionic neurons [3](#page=3). * **Preganglionic neuron:** This neuron originates from the brainstem or medulla spinalis [3](#page=3). * **Ganglia:** These are clusters of nerve cell bodies located outside the CNS. Within the ganglia, preganglionic neurons synapse with postganglionic neurons [3](#page=3). * **Postganglionic neuron:** The axon of this neuron integrates with effector tissues and organs, transmitting the final signal [3](#page=3). ### 1.2 Components of the ANS The autonomic nervous system comprises three main components: * Sympathetic system [4](#page=4). * Parasympathetic system [4](#page=4). * Enteric system [4](#page=4). --- # Sympathetic and parasympathetic nervous systems The sympathetic and parasympathetic nervous systems are the two main divisions of the autonomic nervous system (ANS), working in a generally antagonistic manner to regulate involuntary bodily functions and maintain homeostasis [12](#page=12). ### 2.1 Sympathetic nervous system The sympathetic nervous system is often referred to as the 'fight or flight' system. It prepares the body for intense physical activity in response to stressful situations such as trauma, fear, cold, or exercise [10](#page=10) [9](#page=9). #### 2.1.1 Anatomy Sympathetic neurons originate from the thoracic and lumbar regions of the spinal cord (T1-L2). Preganglionic neurons in this system are short, synapsing in ganglia, while the postganglionic neurons are long. The sympathetic system tends to act as a whole, activating many effector organs simultaneously [5](#page=5). #### 2.1.2 Neurotransmitter The primary neurotransmitter of the sympathetic nervous system is noradrenaline (NA), also known as norepinephrine (NE) [5](#page=5) [9](#page=9). #### 2.1.3 Effects of sympathetic stimulation Stimulation of the sympathetic nervous system leads to a range of physiological responses: * **Mydriasis**: Dilation of the pupils. This is mediated by $\alpha_1$ adrenergic receptors [11](#page=11) [35](#page=35). * **Increased heart rhythm and contractility**: The heart beats faster and with greater force, mediated by $\beta_1$ adrenergic receptors. This relates to positive chronotropic and inotropic effects [11](#page=11) [36](#page=36). * **Increased blood flow to muscles**: Blood is diverted from less essential organs to skeletal muscles to prepare for action [11](#page=11). * **Decreased blood flow to organs**: Non-essential organs receive less blood supply during a 'fight or flight' response [11](#page=11). * **Bronchodilation**: Airways in the lungs widen, allowing for increased oxygen intake, mediated by $\beta_2$ adrenergic receptors [11](#page=11) [36](#page=36). * **Piloerection**: Erection of hairs, causing goosebumps. This is mediated by $\alpha_1$ adrenergic receptors [11](#page=11) [35](#page=35). * **GI tract and bladder relaxation**: Muscles in the digestive tract and bladder relax, inhibiting their usual functions during a crisis [11](#page=11). * **Vasoconstriction**: Contraction of blood vessels, particularly in the skin and viscera, mediated by $\alpha_1$ and $\alpha_2$ adrenergic receptors [35](#page=35). * **Ejaculation**: A function mediated by $\alpha_1$ adrenergic receptors [35](#page=35). * **Inhibition of NE release**: $\alpha_2$ receptors can inhibit further release of norepinephrine [35](#page=35). * **Decreased insulin release**: Mediated by $\alpha_2$ adrenergic receptors [35](#page=35). * **Increased renin synthesis**: Stimulated by $\beta_1$ adrenergic receptors, influencing blood pressure regulation [36](#page=36). * **Stimulates lipolysis**: Breakdown of fats, mediated by $\beta_1$ and $\beta_3$ adrenergic receptors [36](#page=36). * **Uterine relaxation**: Mediated by $\beta_2$ adrenergic receptors [36](#page=36). * **Dopamine D1 effects**: Relaxation of renal vessels [36](#page=36). #### 2.1.4 Tissues with sympathetic-only innervation Some tissues receive innervation exclusively from the sympathetic nervous system: * Adrenal medulla [17](#page=17). * Kidneys [17](#page=17). * Pilomotor muscles [17](#page=17). * Sweat glands [17](#page=17). ### 2.2 Parasympathetic nervous system The parasympathetic nervous system is known as the 'rest and digest' system. It is involved in functions such as resting, eating, and digesting [12](#page=12). #### 2.2.1 Anatomy Parasympathetic preganglionic neurons originate from the cranial nerves and the sacral region of the spinal cord (S2-4). Their ganglia are located near, or even within, the effector organs. Consequently, parasympathetic preganglionic neurons are long, while postganglionic neurons are short. A significant portion of parasympathetic nerve fibers are carried by the vagus nerve [6](#page=6). #### 2.2.2 Neurotransmitter The neurotransmitter of the parasympathetic nervous system is acetylcholine (ACh) [6](#page=6). #### 2.2.3 Effects of parasympathetic stimulation (Cholinergic effects) Parasympathetic stimulation elicits various effects, primarily mediated by muscarinic receptors: * **Myosis**: Constriction of the pupil (circular muscle) [33](#page=33). * **Near vision focus**: Contraction of the ciliary muscle for accommodation [33](#page=33). * **Bronchospasm**: Constriction of the airways [33](#page=33). * **Cardiac depression**: Decreased heart rate and contractility, primarily mediated by M2 muscarinic receptors [33](#page=33). * **Increased secretions**: Stimulation of glands to produce secretions [33](#page=33). * **Sphincter relaxation**: Relaxation of smooth muscle sphincters [33](#page=33). * **Increased GI movements**: Enhanced motility of the gastrointestinal tract [33](#page=33). * **Erection**: A physiological response mediated by parasympathetic stimulation [33](#page=33). These muscarinic effects can be inhibited by atropine [33](#page=33). Nicotinic effects, also mediated by acetylcholine but not exclusively parasympathetic, include: * **Striated muscle contraction**: While not an autonomic function, it's a notable effect of ACh at nicotinic receptors [33](#page=33). * **Adrenaline secretion from the adrenal medulla**: ACh stimulates the release of adrenaline from the adrenal medulla via nicotinic receptors [33](#page=33). These nicotinic effects cannot be inhibited by atropine [33](#page=33). #### 2.2.4 Functional relationship with the sympathetic system The parasympathetic system generally works individually, with nerves to each organ activated separately, unlike the sympathetic system's widespread activation. It usually provides complementary and balancing effects to the sympathetic system, ensuring homeostasis. For most organs, the parasympathetic system exerts opposite effects to those of the sympathetic system, a concept known as dual innervation. In organs with dual innervation, one system is typically dominant, meaning its efficiency is higher in that specific organ. For instance, the parasympathetic system is dominant in the heart, while the sympathetic system is dominant in blood vessels [12](#page=12) [16](#page=16). > **Tip:** Understanding the specific neurotransmitters (NE for sympathetic, ACh for parasympathetic) and their receptor subtypes (adrenergic and cholinergic) is crucial for predicting organ responses. Remember that while NE is the primary sympathetic neurotransmitter, ACh is used at the preganglionic synapse in both systems. > **Example:** When you encounter a threat, your sympathetic system increases your heart rate and dilates your bronchioles (fight or flight). Later, when you are resting and eating, your parasympathetic system slows your heart rate and increases digestive activity (rest and digest). These opposing actions ensure your body can respond dynamically to different demands. --- # Enteric nervous system and central nervous system influence The enteric nervous system acts as an independent "brain of the intestine" that regulates gastrointestinal functions, with its activity also modulated by the central nervous system through reflex arcs and emotional responses [13](#page=13) [8](#page=8). ### 3.1 The enteric nervous system The enteric nervous system (ENS) is considered the third division of the autonomic nervous system (ANS). It is often referred to as the "brain of the intestine" due to its capacity for independent regulation of gastrointestinal functions, separate from the central nervous system (CNS). The ENS comprises nerves that stimulate the gastrointestinal tract, pancreas, and gallbladder. Its primary roles include regulating GI motility and the microcirculation of exocrine and endocrine secretions. While operating independently, ENS activity is also modulated by the sympathetic and parasympathetic nervous systems [8](#page=8). ### 3.2 Central nervous system influence on autonomic functions The ANS functions as a motor system, exclusively containing efferent neurons. However, for effective regulation, the CNS requires afferent neurons to transmit information from autonomic targets in the periphery back to various central sites for evaluation. Consequently, ANS activity is partly regulated by the CNS [13](#page=13). #### 3.2.1 Reflex arcs A significant portion of afferent impulses are involuntarily processed and converted into reflex responses. For instance, a drop in blood pressure (BP) is detected by pressure-sensitive neurons, known as baroreceptors, located in the heart, vena cava, aortic cavity, and carotid sinuses. These baroreceptors reduce signaling to the cardiovascular (CV) centers in the brain. In response to this signal, a reflex is initiated where the sympathetic system is activated, and the parasympathetic system is suppressed, thereby stabilizing the situation. Each ANS reflex arc typically comprises one afferent and one efferent neuron [14](#page=14). > **Tip:** Remember that while the ANS is a motor system with efferent neurons, the CNS relies on afferent neurons to receive sensory feedback from autonomic targets, enabling a closed-loop control system. #### 3.2.2 Emotions Strong emotional states, such as anger, fear, hatred, disgust, euphoria, and pleasure, have the capacity to influence the ANS [15](#page=15). > **Example:** Experiencing intense fear can trigger a "fight-or-flight" response mediated by the sympathetic nervous system, leading to increased heart rate, altered blood flow, and other physiological changes. Conversely, feelings of pleasure or relaxation can activate the parasympathetic "rest-and-digest" response. --- # Neurotransmitters, receptors, and chemical communication This section details the mechanisms of chemical signaling between neurons, focusing on the synthesis, release, termination, and receptor interactions of key neurotransmitters like acetylcholine and noradrenaline. ### 4.1 Principles of chemical communication Chemical communication between cells relies on neurotransmitters to transduce signals. Neurotransmitters are hydrophilic and cannot cross the cell membrane, thus acting on membrane-bound receptors. The release of neurotransmitters from the axon terminal is triggered by calcium influx upon arrival of an action potential, leading to exocytosis into the synaptic gap where they bind to postsynaptic receptors. The activity of neurotransmitters is terminated through various mechanisms [20](#page=20) [23](#page=23). ### 4.2 Key neurotransmitters and their systems * **Noradrenaline (NE):** Primarily affects the sympathetic nervous system and acts on adrenergic receptors [20](#page=20). * **Acetylcholine (Ach):** Primarily affects the parasympathetic nervous system and acts on cholinergic receptors [20](#page=20). There are two specific sites that receive sympathetic stimulation but utilize Ach as their neurotransmitter: the adrenal medulla and eccrine sweat glands [21](#page=21). ### 4.3 Neurotransmitter receptors Receptors are proteins that recognize and bind to specific ligands, such as neurotransmitters [23](#page=23). #### 4.3.1 Cholinergic receptors Cholinergic receptors are classified into two main types: muscarinic and nicotinic receptors [23](#page=23). * **Muscarinic receptors:** * There are five subtypes: M1, M3, M5 which are Gq-coupled, and M2, M4 which are Gi-coupled [25](#page=25). * These receptors are widespread throughout the body [26](#page=26). * Affinity: Muscarinic > Ach [27](#page=27). * **Nicotinic receptors:** * These receptors are coupled directly with ion channels [25](#page=25). * They are found in five key regions: sympathetic and parasympathetic ganglia, the brain, the neuromuscular junction, the adrenal medulla, and Renshaw cells in the medulla spinalis [26](#page=26). * Upon activation, they allow the passage of sodium ($Na^+$) and calcium ($Ca^{2+}$) ions into the cell [28](#page=28). * Affinity: Nicotine > Ach [27](#page=27). #### 4.3.2 Adrenergic receptors Adrenergic receptors are affected by noradrenaline (NE) and epinephrine (Epi). All adrenergic receptors are G protein-coupled receptors (GPCRs) [24](#page=24). * **Alpha ($\alpha$) receptors:** * $\alpha1$ receptors are Gq-coupled and typically mediate constriction [24](#page=24). * $\alpha2$ receptors are Gi-coupled and typically mediate inhibition [24](#page=24). * **Beta ($\beta$) receptors:** * All $\beta$ receptors are Gs-coupled and typically mediate stimulation or relaxation [24](#page=24). * Subtypes include $\beta1$ and $\beta2$. * Affinity for Adrenergic ligands: * General Alpha: Epi > NE >>> Isoproterenol [27](#page=27). * General Beta: Isoproterenol > Epi > NE [27](#page=27). * $\beta1$: Epi = NE [27](#page=27). * $\beta2$: Epi > NE [27](#page=27). #### 4.3.3 Receptor affinity and drug effects Neurotransmitters and drugs exhibit varying affinities for different receptors. The localized distribution of receptors also influences drug effects. Different drugs are selected based on their specific indications and receptor affinities [27](#page=27). ### 4.4 Receptor activation pathways The intracellular signaling cascades activated by receptor binding differ based on the receptor's G protein coupling: * **Gs and Gi coupled receptors:** These utilize adenylate cyclase (AC) as a secondary messenger. Gs activation stimulates AC, while Gi inhibits it. This regulation affects intracellular phosphorylation, leading to cellular functional changes [28](#page=28). * **Gq-coupled receptors:** These employ the inositol trisphosphate/diacylglycerol (IP3/DAG) system as secondary messengers. This pathway leads to increased intracellular calcium ($Ca^{2+}$) release and subsequent phosphorylation [28](#page=28). * **Nicotinic receptors:** These are ionotropic receptors, directly modulating ion channel permeability for $Na^+$ and $Ca^{2+}$ [28](#page=28). ### 4.5 Neurotransmitter synthesis and termination #### 4.5.1 Acetylcholine synthesis and termination The synthesis and termination of acetylcholine involve several steps: 1. **Choline uptake:** Choline is transported into the neuron. This process can be blocked by hemicholinium [29](#page=29). 2. **Acetylcholine synthesis:** Choline interacts with acetyl CoA, catalyzed by choline acetyltransferase, to form Ach [29](#page=29). 3. **Vesicular storage:** Ach is stored in synaptic vesicles. This storage can be blocked by vesamicol [29](#page=29). 4. **Release:** Ach is released into the synaptic gap. This release can be inhibited by botulinum toxin [29](#page=29). 5. **Receptor binding:** Ach acts on postsynaptic receptors [29](#page=29). 6. **Degradation:** Ach is rapidly degraded in the synapse by acetylcholinesterase [29](#page=29). 7. **Choline reuptake:** The resulting choline is reuptaken into the cell for reuse, marking a rate-limiting step [29](#page=29). Unlike noradrenaline, Ach is degraded in the synapse [29](#page=29). #### 4.5.2 Noradrenaline synthesis and termination The synthesis of noradrenaline involves the following enzymatic conversions: 1. **Tyrosine to L-DOPA:** Tyrosine is converted to L-DOPA by tyrosine hydroxylase. This step is rate-limiting and can be blocked by methytyrosine [30](#page=30). 2. **L-DOPA to Dopamine (DA):** L-DOPA is converted to DA by DOPA decarboxylase. This conversion can be inhibited by carbidopa [30](#page=30). 3. **Dopamine to Noradrenaline (NE):** DA is converted to NE by $\beta$-hydroxylase. This step can be blocked by disulfiram [30](#page=30). In the adrenal medulla, NE can be further converted to epinephrine (Epi) by phenylethanolamine N-methyltransferase (PNMT), a process induced by cortisol [30](#page=30). The termination of NE's action occurs through reuptake mechanisms and enzymatic degradation: 1. **Vesicular storage:** Synthesized NE is stored in vesicles, a process that can be blocked by reserpine [31](#page=31). 2. **Release:** Upon arrival of an action potential at the terminal, NE is released into the synapse. Guanethidine can block this release [31](#page=31). 3. **Termination:** After exerting its effect, released NE is removed by neuronal reuptake (uptake-1) or extraneuronal uptake (uptake-2) [31](#page=31). * **Uptake-1:** This process is blocked by cocaine and tricyclic antidepressants (TCAs). Within the neuron, NE is degraded by monoamine oxidase (MAO) enzymes [31](#page=31) [32](#page=32). * **Uptake-2:** This process is blocked by corticosteroids. In this pathway, NE is degraded by catechol-O-methyl transferase (COMT) [32](#page=32). ### 4.6 Catecholamines Catecholamines are molecules characterized by a 3,4-dihydroxybenzene group. Examples include epinephrine (Epi), noradrenaline (NE), dopamine (DA), dobutamine, and isoproterenol. These compounds cannot cross the blood-brain barrier (BBB) [34](#page=34). ### 4.7 Ganglia Ganglia, both sympathetic and parasympathetic, contain nicotinic receptors. Stimulation of these nicotinic receptors increases both sympathetic (S) and parasympathetic (PS) activities. However, overstimulation can lead to the suppression of both activities. The somatomotor system does not possess ganglia [19](#page=19). --- # Somatic nervous system The somatic nervous system is a voluntary system responsible for controlling skeletal muscles through direct neural connections and relaying sensory information from the periphery to the central nervous system [18](#page=18). ### 5.1 The somatomotor system The somatomotor system constitutes the efferent component of the somatic nervous system, which directs motor commands to skeletal muscles [18](#page=18). * **Neuron Structure:** The neurons of the efferent somatic nervous system extend directly from the central nervous system to the skeletal muscles they innervate. This pathway is characterized by [18](#page=18): * Consisting of a single nerve fiber [18](#page=18). * Lacking any ganglia along the pathway [18](#page=18). * Being myelinated, which facilitates rapid signal transmission [18](#page=18). * **Speed of Effect:** The direct, single-neuron pathway and myelination contribute to a rapid response [18](#page=18). * **Voluntary Control:** This system is considered voluntary, meaning its actions are consciously controlled by the individual [18](#page=18). ### 5.2 The somatosensory system The somatosensory system comprises the afferent neurons that convey sensory information from the body's periphery back to the central nervous system. This system allows for the perception of touch, pain, temperature, and proprioception [18](#page=18). --- ## Common mistakes to avoid - Review all topics thoroughly before exams - Pay attention to formulas and key definitions - Practice with examples provided in each section - Don't memorize without understanding the underlying concepts

| Term | Definition | |------|------------| | Autonomic nervous system (ANS) | A division of the peripheral nervous system that regulates involuntary bodily functions such as heart rate, digestion, and breathing, operating without conscious control. | | Central nervous system (CNS) | The part of the nervous system comprising the brain and spinal cord, responsible for processing information and coordinating bodily activities. | | Peripheral nervous system (PNS) | The part of the nervous system outside the brain and spinal cord, consisting of nerves that connect the CNS to the rest of the body. | | Somatic nervous system | A division of the peripheral nervous system that controls voluntary movements by transmitting signals to skeletal muscles. | | Preganglionic neuron | A neuron in the ANS whose cell body is located in the CNS and whose axon extends to an autonomic ganglion. | | Postganglionic neuron | A neuron in the ANS whose cell body is located in an autonomic ganglion and whose axon extends to an effector organ. | | Autonomic ganglion | A cluster of nerve cell bodies of postganglionic neurons located outside the CNS. | | Sympathetic system | The division of the ANS that prepares the body for "fight or flight" responses, characterized by increased heart rate, blood pressure, and alertness. | | Parasympathetic system | The division of the ANS that promotes "rest and digest" functions, characterized by decreased heart rate, increased digestion, and energy conservation. | | Enteric system | A complex network of neurons within the walls of the gastrointestinal tract that regulates digestive functions, often referred to as the 'brain of the intestine'. | | Neurotransmitter | A chemical messenger released by a neuron to transmit a signal to a target cell, such as another neuron, muscle cell, or gland cell. | | Noradrenaline (NA, NE) | A neurotransmitter and hormone primarily associated with the sympathetic nervous system, mediating the "fight or flight" response. | | Acetylcholine (Ach) | A neurotransmitter found in both the CNS and PNS, playing a key role in muscle contraction, learning, memory, and parasympathetic nervous system functions. | | Mydriasis | Dilation of the pupil of the eye, often caused by sympathetic stimulation. | | Bronchodilation | Widening of the airways in the lungs, typically a response to sympathetic stimulation. | | Piloerection | The "goosebumps" response, where the small muscles attached to hair follicles contract, causing hairs to stand on end, mediated by the sympathetic system. | | Reflex arc | A neural pathway that controls a reflex, typically involving a sensory neuron, interneuron (in some cases), and a motor neuron. | | Adrenergic receptors | Receptors in the body that bind to catecholamines like epinephrine (adrenaline) and norepinephrine (noradrenaline). | | Cholinergic receptors | Receptors in the body that bind to acetylcholine. | | Muscarinic receptors | A type of cholinergic receptor that is a G protein-coupled receptor, found in various tissues including smooth muscle, cardiac muscle, and glands. | | Nicotinic receptors | A type of cholinergic receptor that is a ligand-gated ion channel, found at the neuromuscular junction, in autonomic ganglia, and in the CNS. | | Gq-coupled receptors | G protein-coupled receptors that activate phospholipase C, leading to the production of inositol trisphosphate ($IP_3$) and diacylglycerol (DAG), which increase intracellular $Ca^{2+}$ and activate protein kinase C. | | Gi-coupled receptors | G protein-coupled receptors that inhibit adenylate cyclase, leading to a decrease in cyclic AMP ($cAMP$) levels within the cell. | | Gs-coupled receptors | G protein-coupled receptors that stimulate adenylate cyclase, leading to an increase in cyclic AMP ($cAMP$) levels within the cell. | | Adenylate cyclase (AC) | An enzyme that catalyzes the formation of cyclic AMP (cAMP) from ATP, acting as a second messenger in many cellular signaling pathways. | | Ionotropic receptors | Receptors that are coupled directly to an ion channel, meaning their activation causes the channel to open or close, altering ion flow across the cell membrane. | | Acetylcholinesterase | An enzyme that breaks down acetylcholine in the synaptic cleft, terminating its action. | | Monoamine oxidase (MAO) | An enzyme that breaks down monoamine neurotransmitters, such as noradrenaline and dopamine, primarily within the neuron. | | Catechol-O-methyl transferase (COMT) | An enzyme that metabolizes catecholamines, including noradrenaline and dopamine, in the extraneuronal space. | | Catecholamines | A group of monoamine compounds, including epinephrine, norepinephrine, and dopamine, characterized by a catechol structure. |