Sympathetic nervous system pathways

Enhanced automaticity occurs in hypoxia, hypokalemia, hypercarbia, excessive sympathetic nervous system stimulation, or high concentrations of catecholamines. These conditions may lead to arrhythmias. Decreased automaticity may also lead to production of arrhythmias by enhancing ectopic activity in latent pacemakers (ectopic foci) or by altering conductivity and refractoriness in conduction pathways of myocardium. 

Because of its motor, i.e., activating effect on vascular smooth muscle and its inhibitory effect on intestinal smooth muscle, the sympathetic nervous system has been cast into the role of the component of the nervous system that executes control of visceral function in times of physical emergency for the organism. The phrase fight or flight has been often used to describe the circumstances in which the adrenergic transmitters of the sympathetic system are dominant over the cholinergic parasympathetic system. This concept is perhaps oversimplified but it has the utility of a first approximation of how the two components of the ANS interact in the periphery. Sensory inputs which lead to increased blood pressure, for example, activate the sympathetic pathways. 

Development and progression of heart failure involves activation of neurohormonal pathways, including the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS). 

The sympathetic nervous system (SNS) and the hypothalamic-pituitary axis work together as important modulators of the immune system after exposure to stressors. Norepinephrine (NE) and epinephrine (EPI) (catecholamines from the SNS) and neuroendocrine hormones modulate a range of immune cell activities, including cell proliferation, cytokine and antibody production, lytic activity, and migration. This chapter will focus on these two major pathways of brain-immune signaling, briefly summarizing the evidence for SNS and hypothalamic-pituitary-adrenal (HPA) modulation of immune function, their influence on immune-mediated diseases, immune modulation in aging, and early life influences on these pathways. 

Known most famously for their part in the fight or flight response to a threat, challenge or anger, adrenaline (epinephrine) and dopamine from the adrenal medulla and noradrenaline (norepinephrine), mainly from neurones in the sympathetic nervous system are known collectively as catecholamines. Synthesis follows a relatively simple pathway starting with tyrosine (Figure 4.7). 

Norepinephrine A neurotransmitter that is important in certain brain pathways and in the terminal synapses of the sympathetic nervous system (SYN noradrenaline). 

The most well known of the naturally occurring phenethylamine derivatives (Table I) are the transmitters of the sympathetic nervous system, epinephrine, norepinephrine, and dopamine. All these compounds are 3,4-dioxygenated in the aromatic nucleus and are collectively known as the catecholamines. Norepinephrine is the transmitter of most sympathetic postganglionic fibers, dopamine is the predominant transmitter of the mammalian extrapyramidal system and of several mesocortical and mesolimbic neuronal pathways, and epinephrine is the major hormone of the adrenal medulla (363). The literature that has accumulated on the action of these compounds in higher animals is enormous. Metanephrine and normetanephrine are known from animals as deactivated metabolites of epinephrine and norepinephrine that result from the action of the enzyme catechol O-methyltransferase (364). 

Lesions of the retina, optic nerve, chiasm, and optic tract do not cause anisocoria. A lesion in the midbrain produces a subtle and transient anisocoria. However, most neurologic causes of anisocoria involve lesions in the efferent pupillary pathway. These defects arise due to asymmetric disruptions of the parasympathetic or sympathetic nervous systems that innervate the iris.The presence of anisocoria may help to limit a lesion to this pathway but does not localize the lesion s location within that pathway. 

The activation of the stress systems affects all tissues of the organism, and the peripheral immune system is no exception. These effects are mediated through at least tw o pathways via the HPA axis and by virtue of the innervation of lymphatic tissues by autonomic nerve fibers, especially from the sympathetic nervous system. All lymphoid tissues, primary (bone marrow and thymus) as well as secondary (spleen, lymph nodes, and gut-associated lymphoid tissue) are innervated by sympathetic nerve fibers. As discussed above, most lymphoid cells express catecholamine receptors, including B-lymphocytes, CD4- and CD 8-positive T cells, dendritic cells, monocytes, and macrophages. 

Biosynthetic pathway inhibitors. In both the central and periphery nervous systems, the biosynthetic pathways for catecholamines, including the sympathetic nervous system transmitter noradrenaline, involve a number of enzymic conversions that may, in principle, be inhibited. There are several inhibitors known that interfere with catecholamine production (e.g, carbidopa or benzerazide) and may therefore act as antisympathetic agents. See dopa decarboxylase inhibitors dopamine P-hydroxylase inhibitors. 

DOPA to dopamine, by the cytosolic enzyme, DOPA decarboxylase. In the central and peripheral nervous systems, dopamine is converted to noradrenaline by dopamine-P-hydroxylase (DBH), which, though a relatively non-specific enzyme, is restricted to catecholamine-synthesizing cells. It can be inhibited by many drugs, which brings the risk of complex drug interactions. In the peripheral sympathetic nervous system, noradrenaline, in turn, is converted to adrenaline, by phenylethylamine N-methyl transferase, so inhibition of DBH can therefore, in principle, slow production of both adrenaline and noradrenaline but normally tyrosine hydroxylase is the rate-limiting step in the synthetic pathway. 

Neurologic pathways in the sympathetic nervous system originate from the thoracic (T1 to T12) and the upper lumbar segments (LI and L2) of the spinal cord. Neurologic pathways in the parasympathetic nervous system originate from cranial nerves III, VII, IX, and X, from the brainstem, and the sacral segments S2, S3, and S4 from the spinal cord. This is why the parasympathetic nervous system is also known as the craniosacral division of the autonomic nervous system. 

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