Deciphering the iron enigma: Navigating the complexities of iron metabolism in critical illness

Abstract

Iron is a double-edged sword! Despite being essential for numerous physiological processes of the body, a dysregulated iron metabolism can result in tissue damage, exaggerated inflammatory response, and increased susceptibility to infection with certain pathogens that thrive in iron-rich environment. During sepsis, there is an alteration of iron metabolism, leading to increased transport and uptake into cells. This increase in labile iron may cause oxidative damage and cellular injury (ferroptosis) which progresses as the disease worsens. Critically ill patients are often complicated with systemic inflammation which may contribute to multiple organ dysfunction syndrome or sepsis, a common cause of mortality in intensive care unit. Originally, ferritin was known to play an important role in the hematopoietic system for its iron storage capacity. Recently, its role has emerged as a predictor of poor prognosis in chronic inflammation and critical illnesses. Apart from predicting the disease outcome, serum ferritin can potentially reflect disease activity as well.

Keywords: Critical illness, Ferritin, Inflammation, Iron, Mortality, Sepsis

Core Tip: Traditionally serum iron parameters including ferritin have served as biomarkers for assessing the iron status. Recently, the spectrum of utility for these markers has widened as tools for assessing inflammation and predicting outcomes in critically ill patients. These markers have been associated with high mortality and poor clinical outcomes in various critical illnesses. Serial measurement of iron parameters, especially in patients admitted to intensive care units, may be used as potential tools to determine worsening and progression towards multiorgan failure. However, their interpretation must be in accordance with the patient's clinical condition and other biochemical parameters, for guiding further treatment to optimize clinical care and prognosis.