02-introduction to the Autononomic Nervous System ANS.pdf

1 INTRODUCTION TO AUTONOMIC CONTROL SYSTEMS Neural part (CNS) : Thoraco-lumbar elaborations and integrati...

1 INTRODUCTION TO AUTONOMIC CONTROL SYSTEMS Neural part (CNS) : Thoraco-lumbar elaborations and integrations outflow sympathetic ganglion nucleus nucleus nucleus parasymp Vagus X effector ganglion receptor system organ mechanical, chemical, contraction, distension, thermal, optical,… T, [CO2],… secretion, gas or fluid exchange,… In physiology and anatomy the autonomic nervous system (ANS) strictly refers to the outflow (alias, efferent) pathways in the peripheral nervous system (ganglia and neural fibres) and the nuclei in central nervous system (CNS) directly driving them. However, in the above scheme, we also emphasize the inflow (alias, afferent) pathways starting from various receptors and the integration nuclei connecting the outflow ones. This to remark the feedback regulation/control overall exerted by the ANS.  2 ELEMENTS OF AUTONOMIC CONTROL SYSTEMS PHYSIOLOGICAL SYSTEM - vital physiological quantities: metabolic activity, temperature, chemical concentrations. RECEPTORS - convert mechanical, chemical, thermal, optical quantities into a neural signal. NUCLEI: in the medulla (brainstem) and diencephalon (hypothalamus, amygdala, …) – elaborations and integrations. SYMPATHETIC OUTFLOW: from the spine (thoraco-lumbar region) through sympathetic ganglia and spinal nerves. PARASYMPATHETIC OUTFLOW: from the medulla through cranial nerves (vagus X) to ganglia at target organs. EFFECTORS - contraction/distension, excretion, conduction time modulations, fluid/gas exchange …  3 GENERAL CHARACTERISTICS Response versatility: homeostasis at cellular level translates to the need of high adaptivity at physiological system level, changing the working point (often referred to as “resetting”) according to activity or environment needs (e.g., heart rate during sleep, rest, standing, exercise, etc.). This set of actions is often called “homeo-dynamics” (sometimes “etherostasis”). Generalised parallelism in both afferent and efferent pathways. Interactions at peripheral level: controlled variables interact with other controlled variables and regulation acts on vastly distributed systems (e.g. arterial tree, digestive tube, chemical compartments in organs …). Interactions at central level: any regulatory activity modulates and is modulated by several other ones. Embedded set points as in any physiological control (note: it is observed that the working points of variables under autonomic control, e.g. heart rate, in the long term display large oscillations within physiological ranges with random walk, self-similar, and 1/f behaviours features; this is likely related to the absence of fixed set-points, differently from artificial control systems). Intrinsic regulation inside the target organs on which autonomic regulation is superimposed. Hierarchical organisation: regulation is performed at several levels. Non-linearity of interactions à self organisation, synergetic actions, compensation à versatility, self-adaptivity, but also crash into pathological behaviours.  4 SYMPATHETIC VS PARASYMPATHETIC Sympathetic and parasympathetic effects are often antagonists (e.g. sympatho/vagal balance on the heart). Sympathetic ↔ “fight/flight/fright” reactions 1. Increase of: - heart rate - arterial pressure - cardiac contractility - conduction velocity - bronchial dilatation (gas exchange), respiratory freq. - pupil dilatation (better visual resolution) - hair erection (it. orripilazione), sweating - dilatation of muscular vessels - glucose metabolism 2. Decrease of: - digestive system motility and excretion, salivation - skin blood flow (it. vasocostrizione cutanea, pallore)  5 Observation: Only the regulation of the outflow to the skin and peripheral vessels is purely sympathetic; in general, all sympathetic actions are balanced by an antagonistic parasympathetic action. EFFECTOR SYMPATHETIC PARASYMPATHETIC SYSTEM activity activity HEART (HR, AP, contractility, ↑ ↓ conduction velocity) RESPIRATORY (Bronchial dilatation, ↑ ↓ respiratory frequency) SIGHT (pupil dilatation) ↑ ↓ HAIR ERECTION, ↑ No effects SWEAT GLANDS Muscular VESSELS (dilatation) ↑ No effects SKIN BLOOD FLOW ↓ No effects DIGESTIVE (motility and excretion, salivation) ↓ ↑ Curiosity: hair erection or goose bumps (it. pelle d’oca) is also said “horripilation” (from Latin). Since it is and effect fight/flight/fright arousals, even in common language it is related to frightening or emotional reactions.  6 AUTONOMIC NERVOUS SYSTEM FUNCTIONAL ANATOMY SCHEME OF SYMPATHETIC AND PARASYMPATHETIC SYSTEMS (from Berne & Levy, Physiology) Left) sympathetic thoracolumbar centers and the outflow pathways (bilateral, not shown). Right) the parasympathetic centers and outflow.  7 Note that: Preganglionic neuron bodies are inside the CNS: a) sympathetic, in the thoraco-lumbar spinal cord (T1-T12 and L1-L2, for this reason “thoracolumbar system” is an alias for sympathetic system); b) parasympathetic, in the brainstem and in the sacral spinal cord Sympathetic (post) ganglionic fibers stem from neuron bodies in the ganglia close to the spine: i) paravertebral chain (fig. sympathetic chain), ii) prevertebral ganglia (fig. collateral ganglions) (celiac, inf. mesenteric, sup. mesenteric) Although the sympathetic nuclei are concentrated in the thoracic and first two lumbar segments of the spine, the paravertebral chain covers all spinal segments, down to the sacral ones (outflow to lower viscera) and up to the cervical ones (outflow to the heart, lungs and head). Some cervical ganglia are fusing two or more segments, this is the case of the stellate ganglion, important for the innervation of the heart. The adrenal medulla can be understood as a “modified sympathetic ganglion”, which is innervated by sympathetic preganglionic fibers as all the others, but releases its neurotransmitter directly in the blood stream, without projecting postganglionic fibers. Parasympathetic preganglionic fibers from the brainstem medulla travel a long way along cranial nerves (mainly the vagus or nerve X) to ganglia attached to the target organs. Thus, the parasympathetic postganglionic fibers are very short.  8 NEURO-TRANSMITTERS Ø CHOLINERGIC response: short duration (≈ 100 ms), due to a rapid disruption of acetylcholine by cholinesterase. Ø PHARMACOLOGIC actions on the Autonomic N. Syst. (examples): MUSCARINE: parasympathomimetic → mimics achetylcholine; ATROPINE: parasympatholytic → cholinergic blockade; PHENILEPHRINE: sympathomimetic → mimics catecholamines; β-BLOCKERS: sympatholytic → adrenergic blockade; (“mimetic”=imitates; “lythic”=disrupts/blocks) Classifications of neurotransmitters/receptors: Cholinergic = via achetylcholine (it. acetilcolina).  9 Adrenergic = via catecholamines: epinephrine (it. adrenalina) and norepinephrine (it. noradrenalina). The classification of both cholingergic and adrenergic receptors (e.g. a, b with subfamilies indicated by the figure) and their distribution in neurons and target organs is beyond our scopes; yet, of primary importance for pharmacologically. SYMPATHETIC vs PARASYMPATHETIC SUMMARY Features Sympathetic Parasympathetic Gray matter of the Brainstem and gray Location of cell lateral horns in the matter of the lateral bodies (somata) thoraco-lumbar spinal horns in the sacral spinal cord (T1-L2) cord (S2-S4) Spinal nerves, Cranial and pelvic Outflow pathways sympathetic nerves, nerves from the CNS splanchnic nerves Paravertebral chain, Ganglia attached to or Ganglia prevertebral g. close to within the effector the CNS (spinal cord) (target) organs Relative axon Short preganglionic, Long preganglionic, length long postganglionic short postganglionic Acetylcholine Acetylcholine both on Transmitters (ganglion) & ganglia and target Norepinephrine (target) Speed of action Long (seconds) Fast (tenths of second) Sympathetic arousal is Selectively directed to Target diffused to all organisms specific organs Neural and humoral Transmission way (epinephrine from Only neural adrenal medulla)  10 HIERARCHICAL STRUCTURE OF CENTRAL INTEGRATION & AUTONOMIC REFLEXES  11 Central (supraspinal) integration modulates autonomic reflexes (brainstem and spinal cord) and sets a link with limbic and endocrine systems. Different structures and centers involved: Ø MEDULLA OBLUNGATA AND PONS (brainstem): rostral and ventro-lateral medulla (RVLM); raphe nuclei; locus coeruleus; nucleus tracti solitari (NTS), nucleus ambiguus. Ø HYPOTHALAMUS: posterior lateral (excitatory: “defense area”); anterior (depressive) Ø LIMBIC SYSTEM: amygdala (excitatory) Ø CEREBRAL CORTEX: insula; prefrontal cortex (excitatory) Integration of supraspinal with spinal centers and the two autonomic outflows: a) parasympathetic, from brainstem through cranial nerves; b) sympathetic, from spinal cord through spinal nerves.  12 The anatomy of above mentioned centers modulating the ANS is shown in this figure. Note that the ANS starts from the medulla (parasympathetic centers) and the spinal cord (thoraco-lumbar sympathetic centers). Integration centers are above the ANS centers. Nonetheless, they are below our conscious cortical processes The autonomic modulation outflow is both humoral (hormones secreted by glands and transported by the blood stream) and neural. Importantly (see next), the adrenal medulla (it., ghiandole surrenali) are also directly driven by sympathetic preganglionic fibers. They release epinephrine (it., adrenalina), which in turn conveys a generalized sympathetic arousal to all target organs. However, the study of endocrine hormonal regulation is beyond the aims of this course.