This document was created by Alex Yartsev ([email protected]); if I have used your data or images and forgot to reference you, please email me. Mechanism of Multiple Organ Dysfunction Syndrome

This entity is a luxury of our enlightened age. In the olden days people never survived long enough to develop this syndrome.

The Definition: “in an acutely ill patient, the function in two or more organ systems altered such that homeostasis cannot be maintained without intervention” Mechanism of pathogenesis

Genetic predisposition Triggering factors Local inflammation Eg. families with genetically low TNF- • Infection alpha levels, or high IL-10 levels • Aspiration • Burns Activation of the innate immune system • Pancreatitis • Massive transfusion Loss of immunological homeostasis: • Hyperthermia failure of anti-inflammatory regulatory • Malignancy mechanisms to contain the local • Hepatic failure inflammatory response • Cardiopulmonary bypass • Reperfusion injury • Visceral ischaemia • Global hypoxia

TEndothelial dysfunction Tissue injury through hypoxia Mitochondrial dysfunction Apoptosis This means, The hypoxia is a result of multiple factors, The decrease in oxygen consumption may Not just mitochondrial lysis, but - increased endothelial permeability, among which is poor lung function, poor be out of proportion to the decrease in also the various cytokines - slowed microcirculation, cardiac output, microvascular insufficiency, oxygen delivery; this is “tissue dysoxia”. released as a part of a systemic - formation of microthrombi, and poor oxygen utilization at the level of It is due to Nitric Oxide and general inflammatory response will be - de-recruitment of capillaries the mitochondria. reactive oxygen species inhibiting the received as apoptotic signals by - and thus decreased tissue perfusion mitochondrial respiratory chain, as well as cells- particularly in the gut, liver, decreasing pyruvate delivery into the kidney and heart. Krebs cycle. The result is anaerobic metabolism, and lactic acidosis. Plus, the The consequences, the clinical features: mitochondria may lyse, releasing calcium - Encephalopathy: delirium, drowsiness, coma. and other proapoptotic factors. - Cardiomyopathy: depressed contractility, decreased lusitropy, decreased afterload and thus decreased coronary perfusion - ARDS as a feature of the generalized microvascular injury, with resulting hypoxia - Renal failure, with subsequent acidosis - Increased intestinal permeability with bacterial and endotoxin translocation - Ileus, pancreatitis, gastric ulceration, acalculous cholecystitis, gut ischaemia - Hepatic dysfunction and thus decreased glyconeogenesis and decreased lactate clearance - Coagulopathy due to both consumption of products in DIC and bone marrow failure

The Outcomes: Mortality 60-98% if 3 or more organs are down for over 1 week, stratified by age. In determining mortality, cardiovascular dysfunction is the single most important organ failure SOFA score at day 6 is more predictive of Day 7 mortality than SOFA score on admission Whatever the cause, 47% of people could not return to work or normal function at 1 year follow-up

From Bersten and Soni’s” Oh's Intensive Care Manual”, 6th Edition