Surgical inflammatory stress: the embryo takes hold of the reins again

Abstract

The surgical inflammatory response can be a type of high-grade acute stress response associated with an increasingly complex trophic functional system for using oxygen. This systemic neuro-immune-endocrine response seems to induce the re-expression of 2 extraembryonic-like functional axes, i.e. coelomic-amniotic and trophoblastic-yolk-sac-related, within injured tissues and organs, thus favoring their re-development. Accordingly, through the up-regulation of two systemic inflammatory phenotypes, i.e. neurogenic and immune-related, a gestational-like response using embryonic functions would be induced in the patient's injured tissues and organs, which would therefore result in their repair. Here we establish a comparison between the pathophysiological mechanisms that are produced during the inflammatory response and the physiological mechanisms that are expressed during early embryonic development. In this way, surgical inflammation could be a high-grade stress response whose pathophysiological mechanisms would be based on the recapitulation of ontogenic and phylogenetic-related functions. Thus, the ultimate objective of surgical inflammation, as a gestational process, is creating new tissues/organs for repairing the injured ones. Since surgical inflammation and early embryonic development share common production mechanisms, the factors that hamper the wound healing reaction in surgical patients could be similar to those that impair the gestational process.

Figure 1

Schematic representation of microcirculation. In a steady state, the arterial blood flow moves through the capillaries, where it’s deoxygenated before reaching the post-capillary venule. The lymphatic drainage from the interstitial space is reduced and there is a dynamic balance between the formation and the elimination of the interstitial fluid (left). When inflammation is produced, the arterial blood flow can’t be deoxygenated, firstly because the epithelium is necrosed and, secondly because the capillaries are also necrosed and/or obstructed. Arterial blood flow bypass through metaarteriolas prevents the post-capillary vein from being exposed to high oxygen levels. In addition, lymphatic flow gains an unusual prominence (middle). The inflamed interstitium could be represented as surrounded by the different types of endothelium that make up microcirculation, as an “endothelial egg”. The venous and lymphatic endothelium acquire higher extension and functionality since the molecular and cellular exchange between the inflamed interstitium and the rest of the body, that is the host, is produced through them. A: artery; BCE: blood capillary endothelium; C: capillary; E: epithelium; HEVE: high endothelial venule endothelium; I: interstitium; L: lymphatic; LE: lymphatic endothelium; Leu: leukocytes; MA: meta-arteriole; NE: necrosed epithelium; PCVE: postcapillary venule endothelium; SC: stem cell.

Figure 2

Surgical stressful inflammatory response. The host organism provides the inflamed interstitium molecules and cells by up-regulating a neurogenic-related axis (NA), a bone marrow-related axis (BMA) and a gut-liver axis (GLA). The molecular and cellular infiltration of the “endothelial egg” induces the development of a new tissue or organ using inflammatory mechanisms. BCE: blood capillary endothelium; C: coagulation; E: epithelium; ESC: endothelial precursor cell; F: fibroblast; HEVE: high endothelial venule endothelium; HSC: hemopoietic stem cell; LE: lymphatic endothelium; Leu: leukocytes; M: microbiome; MSC: mesenchymal stem cell; PCVE: postcapillary venule endothelium; SC: resident stem cell; SG: suprarenal gland.

Figure 3

Schematic representation of normal tissue (left) and pathological (right) tissue when surgical inflammatory stress is developed. Epithelial necrosis triggers an inflammatory response in the interstitium that is restricted by an endothelial barrier made up of the different types of microcirculatory endothelium. BCE: blood capillary endothelium; E: epithelium; HEVE: high endothelial venule endothelium; I:interstitium; LE: lymphatic endothelium; M: microbiome; NE: necrosed epithelium; PCVE: post-capillary venule endothelium.

Figure 4

Schematic representation of early embryonic development. During early embryo development, the extraembryonic mesoderm and the exocoelomic cavity (EC) relate the trophoblast (T) to the amnion and the secondary yolk sac (YS). The existence of two extra-embryonic axes, an exocoelomic-amniotic axis and a trophoblastic-yolk sac axis could be proposed. This would enable the formation of the intraembryonic mesenchymal since they are integrated. These extraembryonic functions are expressed by the host organism when it suffers an injury and focuses on the injured tissue or organ. After these functions are incorporated by the injured tissue or organ, this said tissue or organ acquires the embryonic functional autonomy needed to successfully repair itself. A: amnion; EC: exocoelomic cavity; EM: extraembryonic mesoderm; D: decidua; T: trophoblast; YS: secondary yolk sac.

Figure 5

Comparative representation between the embryo, with its extra-embryonic membranes (left) and the inflamed tissue (right). Recapitulation of the extra-embryonic exocoelomic-amniotic (E-A)- axis and trophoblastic-yolk sac-related (T-YS) axis within the inflamed tissue would allow the development of a new tissue from the intra-embryonic mesoderm, as it occurs during embryonic development. BCE: blood capillary endothelium; E: epithelium; EC: exocoelomic cavity; EM: extra-embryonicmesoderm; F: fibroblast; HEVE: high endothelial venule endothelium; IM: intraembryonic mesenchyma; LE: lymphatic endothelium; Leu: leukocyte; M: microbiome; MC: mast cell; MØ: Macrophage; PCVE: postcapillary venule endothelium; YS: yolk sac.