What are chemical messengers that diffuse through tissue fluid and affect only nearby cells called?

Extracellular Regulation: Microbial, Autocrine, Luminal, Paracrine, Immunologic, Neural, and Endocrine Systems [Malpines]

The complex minute-by-minute regulation of intestinal function is achieved by the intricate coordination of extracellular factors, contributed by the intestinal microbial, autocrine, luminal, paracrine, immunologic, neural, and endocrine systems [MALPINES]. Originally restricted to “PINES,” this definition has been expanded, and although the distinctions between individual regulatory systems are getting blurred because of the considerable and differential crosstalk of the underlying pathways in health and disease states, the nomenclature is nevertheless useful [Fig. 101.11]. These interactions are compounded by factors with overlapping actions, many of them acting through cell-specific multiple receptors linked to varied signaling pathways.

The last decade has seen an explosion of information on the influence of the luminal microbiome in health and disease states [Chapter 3] ranging from traditional infectious diarrheas, includingClostridioides difficile infection [Chapter 112] to obesity [Chapters 7Chapter 7Chapter 8 and8Chapter 7Chapter 8] and amyotropic lateral sclerosis. In addition, luminal mechanical [stroking and stretch] or chemical [toxins] stimuli can activate mechanoreceptors and chemoreceptors, respectively, to in turn activate one or more arms of ALPINES. Within the subepithelium, structural elements of ALPINES, including blood vessels, are in close proximity [seeFig. 101.11], so release of mast cell mediators can easily target neurons and vice versa; this interplay is critical for the minute-by-minute local regulation necessary in the intestine. Although it is possible to define the specific effects of an individual component in-vitro, clinically the regulatory systems are inextricably intertwined. For example, Verner-Morrison syndrome [pancreatic cholera] is classified as an endocrine-mediated diarrhea because pancreatic islet cell tumors produce large amounts of vasoactive intestinal peptide [VIP] [seeChapter 34]. In the healthy adult, however, VIP is not found in the pancreas but is a peptidergic neurotransmitter of the enteric nervous system [ENS] that stimulates epithelial cell secretion and smooth muscle relaxation. In another example, serotonin [5-hydroxytryptamine [5-HT]] is released from mucosal enterochromaffin cells either directly or indirectly by a variety of mechanical, microbial and chemical stimuli, after which it acts via distinct receptors to elicit a plethora of actions ranging from pro-inflammatory to neuroprotective231: on enterocytes to directly stimulate secretion; on myenteric neurons to release acetylcholine [ACh] and elicit migratory contractions; on submucosal neurons to release ACh and calcitonin gene-related peptide to stimulate peristalsis and secretory reflexes; its receptor expression, and therefore function, is influenced by the microbiome.124,125

Conclusions

The endocrine system regulates the complexity of the Life expressing itself in an organized fashion. The endocrine system’s regulation of itself and its calibration by other factors is similarly complex. This ensures a high degree of responsiveness and attunement of metabolic demands to the requirements of the organism. In addition to the classical definition of hormones by location of origin and distance of action, we presented the Endobiogenic notion of hormone function by type of metabolism regulated. A new system of classification of hormones based on both the geometric and political notions of axis were presented, allowing for an expansion of classification of hormones based on complementarity of action rather than vertical control mechanisms. With this notion of association arises the notion of endocrine axial associations, and new concepts of regulation: horizontal and radial. The organization of the endocrine system in this fashion, while conceptual provides a sense of coherence to the notion of how the terrain is managed. For the clinician, it forms the basis of explaining the origins of disorders and dysfunctions, and will provide the foundation for the selection of a rational selection of therapeutic interventions.