Demystifying Medicine Demystifying MedicineSepsis is the body's response to infection — an inflammatory process marked by an elevated heart rate, rapid breathing and abnormal temperature. Even a minor infection, such as strep throat or influenza, can trigger sepsis. It's usually not life-threatening. But complications of sepsis can cause serious illness and death.
Severe sepsis occurs when your natural immune response to an infection goes into overdrive, triggering widespread inflammation and blood clotting in tiny vessels throughout your body. One or more organs may stop working properly or fail. Sepsis can lead to a dangerous drop in blood pressure (septic shock).
About 750,000 people in the United States get severe sepsis each year, and more than 200,000 people die of it. Those at increased risk include older adults, hospital and surgery patients, and people with impaired immune systems. Neonatal sepsis affects a small percentage of newborns, particularly low-birth-weight and premature infants.
Most commonly, bacterial infections lead to sepsis, but it may result from any type of infection — bacterial, viral, parasitic or fungal. Although sepsis often can't be prevented, getting prompt medical care for infections can reduce your risk.
Discovery of antibiotics which killed most forms of microbes lead to anticipation that infectious diseases were about to be eliminated as sources of human illness. This prediction proved to be over-enthusiastic and incorrect. Microbes, which had persisted since life began on earth, adapted to the new drugs, shifted their gene expression, became multi-drug resistant and, in some cases, manifested new and deadly toxins. Staphlococcal and enterobacterial infectious lead the list. Sudden onset of severe enteric, septicemic (blood-born) and tissue necrotizing infections has become commonplace as has recognition of toxicogenic staph, E Coli and other bacteria. Infections due to these agents has become a major health risk of increasing severity and challenge.
Regardless of the cause, acute sepsis is associated with platelet aggregation and consequent local thrombosis and hemorrhage, and defects in the coagulation system. These "coagulopathy" events are life threatening and, for the most part, are poorly understood.
In 1970, Gilbert Ashwell (NIH) and Anatole Morell (Albert Einstein) and colleagues described the first lectin receptor which also resulted in an early description of the process we now recognize as receptor-mediated endocytosis. The receptor was shown to be abundant on the plasma membrane of hepatocytes facing the blood stream. It bound galactose-terminated desialyated plasma glycoprotein's. and was postulated to be the mechanism for their removal. However, despite 35 years of subsequent study by many investigators, the natural substrate(s) for this abundant hepatocye-specific receptor remained unidentified.
In 2008, Marth and colleagues (UCSD) demonstrated the the asialoglycoprotein receptor regulates removal of von Willebrand factor (a critical coagulation component) as well as platelets from the circulation. Infection with Step pneumoniaie produced thrombocytopenia by removing platelets which were desialated by the bacterium's neuraminidase.
Other studies (Stossel, et al.) demonstrated that, on strage, platelets activate an endogenous nuraminidase, and are then endocytosed by hepatocytes through the Ashwell-Morell receptor.
Thus, an important link has been established between the receptor and development of coagulopathy in bacterial sepsis ... 35 years after its discovery.
This web page was last modified on January 12, 2009. For questions about the course, please contact ariasi@mail.nih.gov.