A computational model of liver iron metabolism

Iron is essential for all known life due to its redox properties; however, these same properties can also lead to its toxicity in overload through the production of reactive oxygen species. Robust systemic and cellular control are required to maintain safe levels of iron, and the liver seems to be where this regulation is mainly located. Iron misregulation is implicated in many diseases, and as our understanding of iron metabolism improves, the list of iron-related disorders grows. Recent developments have resulted in greater knowledge of the fate of iron in the body and have led to a detailed map of its metabolism; however, a quantitative understanding at the systems level of how its components interact to produce tight regulation remains elusive. A mechanistic computational model of human liver iron metabolism, which includes the core regulatory components, is presented here. It was constructed based on known mechanisms of regulation and on their kinetic properties, obtained from several publications. The model was then quantitatively validated by comparing its results with previously published physiological data, and it is able to reproduce multiple experimental findings. A time course simulation following an oral dose of iron was compared to a clinical time course study and the simulation was found to recreate the dynamics and time scale of the systems response to iron challenge. A disease state simulation of haemochromatosis was created by altering a single reaction parameter that mimics a human haemochromatosis gene (HFE) mutation. The simulation provides a quantitative understanding of the liver iron overload that arises in this disease. This model supports and supplements understanding of the role of the liver as an iron sensor and provides a framework for further modelling, including simulations to identify valuable drug targets and design of experiments to improve further our knowledge of this system

Acute kidney injury caused by intravascular hemolysis after mechanical thrombectomy.

A 43-year-old African-American female (gravida 5 para 0) with an 8-week intrauterine pregnancy presented to the emergency room with crampy abdominal pain, shortness of breath, and shoulder pain. She had normal renal function on admission. CT angiography of the chest revealed bilateral pulmonary emboli; therefore, the AngioJet (Possis Medical, Inc., Minneapolis, MN) device was used to perform mechanical thrombolysis. The patient subsequently developed hyperkalemia, red urine and anuria.Physical examination, measurement of serum creatinine level and electrolytes, dipstick urinalysis and centrifugation of urine and blood.Acute kidney injury due to hemoglobinuria as a result of non-immune-mediated intravascular hemolysis following the use of a percutaneous mechanical thrombectomy device (AngioJet).Hydration, alkalinization of urine and initiation of hemodialysis (temporarily switched to continuous venovenous hemodiafiltration). Urine output improved after the 20th day of hospitalization, at which point dialysis was discontinued. The patient's renal function completely recovered by day 25