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Figure 1: CIP and CIM represent a continuum of neurogenic and myogenic changes of varying severity and course and are an integral part of the same process that leads to multi-organ dysfunction in critical illness. (a) In CIP, cytokines and endotoxins released during sepsis, along with hypoxemia, damage the blood nerve barrier and increase permeability of the endoneurial microvasculature. This releases toxic substances into the nerve ends. Hyperglycemia and hypoalbuminemia induce oedema, compromising the microcirculation to peripheral nerves and leading to distal nerve ischemia. Interleukins and cytokines also affect mitochondrial use of oxygen, causing adenosine triphosphate (ATP) depletion. This impairs nutrient transport from the cell body, through the axons, to the distal portion of nerves. All these factors culminate in axonal degeneration. (b) In CIM, several factors negatively affect muscle structure and function like: (1) Impaired microcirculation, nutritional deficiency, inflammatory mediators (TNF-α, IL -1,6 and GDF-15), denervation, endocrine stress and immobilisation result in decreased protein synthesis and increased protein breakdown, especially myosin. (2) Deficient autophagy [a cellular housekeeping system that removes damaged large organelles and protein aggregates] may be a mediator. (3) Denervation potentiates steroid receptor upregulation causing thick filament loss. Denervation is potentiated by concomitant NMBA usage. (4) An altered intracellular calcium homeostasis, affects the excitation–contraction coupling. (5) Oxidative stress and mitochondrial dysfunction cause ATP depletion and hence bioenergetic failure. (6) Sodium channel dysfunction induces muscle membrane non-excitability

Figure 1: CIP and CIM represent a continuum of neurogenic and myogenic changes of varying severity and course and are an integral part of the same process that leads to multi-organ dysfunction in critical illness. (a) In CIP, cytokines and endotoxins released during sepsis, along with hypoxemia, damage the blood nerve barrier and increase permeability of the endoneurial microvasculature. This releases toxic substances into the nerve ends. Hyperglycemia and hypoalbuminemia induce oedema, compromising the microcirculation to peripheral nerves and leading to distal nerve ischemia. Interleukins and cytokines also affect mitochondrial use of oxygen, causing adenosine triphosphate (ATP) depletion. This impairs nutrient transport from the cell body, through the axons, to the distal portion of nerves. All these factors culminate in axonal degeneration. (b) In CIM, several factors negatively affect muscle structure and function like: (1) Impaired microcirculation, nutritional deficiency, inflammatory mediators (TNF-α, IL -1,6 and GDF-15), denervation, endocrine stress and immobilisation result in decreased protein synthesis and increased protein breakdown, especially myosin. (2) Deficient autophagy [a cellular housekeeping system that removes damaged large organelles and protein aggregates] may be a mediator. (3) Denervation potentiates steroid receptor upregulation causing thick filament loss. Denervation is potentiated by concomitant NMBA usage. (4) An altered intracellular calcium homeostasis, affects the excitation–contraction coupling. (5) Oxidative stress and mitochondrial dysfunction cause ATP depletion and hence bioenergetic failure. (6) Sodium channel dysfunction induces muscle membrane non-excitability