Systemic Inflammatory Response Syndrome


By Barry C. Fox, M.D.University of Wisconsin

To meet the criteria for Systemic Inflammatory Response Syndrome (SIRS), the following symptoms are necessary: A temperature higher than 101 degrees; a heart rate greater than 90 beats/minute; a respiratory rate higher than 20 breaths/minute; a white blood cell count that’s either higher than 12,000 or less than 4000. Is this condition treatable?

An X ray image of a patient with septic shock and systemic inflammatory response.
People die of sepsis despite successful antibiotic treatment. (Image: Good Image Studio/Shutterstock)

Sepsis Syndrome or Systemic Inflammatory Response

Sepsis is a syndrome, not a specific clinical entity. It’s actually part of a broader entity known as systemic inflammatory response syndrome, abbreviated SIRS. To have sepsis, the cause of SIRS has to be an infection. When the systolic or top blood pressure number is measured below 90, the condition is further defined as septic shock. 

Even with antibiotics, patients still die of sepsis despite successful antibiotic eradication of the inciting germ. The reason that death may occur in spite of correct antibiotic treatment is that infections are complicated by dysfunction of the body organs, including the brain, heart, lungs, and kidneys.

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Pro-Inflammatory, Anti-Inflammatory and the Clinical Outcome

Invading germs not only causes septic shock themselves, but infection also triggers physiological changes that result in a complex and dynamic interplay of chemical mediators. It’s the balance between evil and good, or essentially pro-inflammatory and counter anti-inflammatory events that determine the clinical outcome. 

In general, pro-inflammatory responses are directed toward eliminating the germs responsible for collateral tissue damage. Anti-inflammatory responses attempt to limit tissue injury, but may reduce the ability to fight off the germs.

An image of a person's hand holding packs of antibiotic capsules.
Antibiotics lead to the destruction of more bacteria, consequently releasing more endotoxins. (Image: Fahroni/Shutterstock)

When gram-positive bacteria are involved, parts of the cell wall components, such as peptidoglycans, are responsible for inducing the septic response. Gram-negative bacteria have different cell wall components. Endotoxin, containing Lipid A, triggers this response.

Ironically, antibiotics used for gram-negative bacteria can paradoxically release more endotoxin as more bacteria are being destroyed, and higher levels of endotoxin are associated with worse patient outcomes.

Effect of Cytokines on Clinical Outcome

When these microbial triggers are recognized by the immune system, activation of both inflammatory and anti-inflammatory immune mediators, known as cytokines, occurs. Two of the first cytokines to be implicated in sepsis are tumor necrosis factor or TNF, and interleukin-1, abbreviated IL-1, and there are many more. 

Both are involved in local inflammation, white blood cell recruitment, and the generation of fever. Higher levels of these two circulating cytokines showed a correlation with worse outcomes. Blocking the effects of IL-1 and TNF in animal models of sepsis led to improved outcomes.

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2001 Outbreak of Sepsis Syndrome

Let’s look at a sepsis example using the anthrax germ. Bacillus anthracis can exist as spores, and in 2001, when news media personnel opened envelopes with anthrax spores, they were easily inhaled and transmitted to the lower portions of the airways, the alveolar space, where the inflammatory response for pneumonia occurs.

An illustration of 'bacillus anthracis', the culprit for anthrax
Anthrax spores are easily inhaled. They cause pneumonia and lead to death. (Image: Kateryna Kon/Shutterstock)

Next, the immune system lung macrophages recognize the spores as a foreign invader. They stimulate the production of cytokines to attract many types of cells and antibodies to the lung. Inflammation also involves the influx of fluid, so the lungs become filled with fluid. 

The pro-inflammatory cytokines may unintentionally destroy the linings of the lung space. This can lead to clogging of the smaller blood vessels of the lung, leading to bleeding. At this time, the victim would be short of breath and coughing up blood.

When Anthrax Germs Enter the Body

Anthrax produces three protein exotoxins into the tissues. One is known as cell-binding protein, the second is edema factor, and the last is a lethal factor. These three exotoxins act together, causing physiological changes. They collaborate to gain entry into the cytoplasm of cells. 

Once inside a cell, the exotoxins disrupt protein synthesis, leading to cell death, and the toxins may also have a direct effect on cells, causing cellular death. When antibiotics are given, the cell wall components of the bacteria break apart, further stimulating an immune response. 

This leads to more fluid and impairment of the exchange of oxygen in the lungs. The anthrax toxin would also lead to depression in the heart’s ability to pump blood to the major organs of the body, reducing blood pressure, and this can deprive the brain of oxygen and cause confusion and coma. 

Simultaneously, the ability of the kidneys to filter waste products of the body is diminished, leading to an accumulation of impurities in the blood. This results in changes to both the acid-base status of the blood and the amounts of sodium and potassium in the blood. The effective antibiotic against anthrax is ciprofloxacin.

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The Bacterial Infection of the Heart

There is one special case of a bloodstream infection known as endocarditis, an infection of the inner layer of the heart. The heart normally has four chambers, separated from one another by four heart valves that control the flow of blood between different chambers. 

When germs invade the bloodstream, they have the ability to latch onto any heart valve and induce heart infection. Some bacteria are much more adept at this task than others, and staph aureus is one such bacteria. Once the germs have attached themselves to a heart valve, they start to grow exponentially, and left untreated, may destroy the heart valve and damage heart tissue. 

Eventually, individuals become ill and seek medical attention, and a diagnosis can be made by culturing the blood for bacteria. Now, it may take 4-6 weeks before the medical suspicion is high enough to even get blood cultures performed to make a diagnosis.

Nature has a number of insidious bacteria that can lead to slow progression of the disease process. So, it is very important to consult a doctor at the right time and begin the treatment.

Common Questions about Systemic Inflammatory Response Syndrome

Q: What is Sepsis syndrome?

Sepsis syndrome is part of SIRS or Systemic Inflammatory Response Syndrome. Sepsis syndrome happens when the cause of the systemic inflammatory response is a bacterial infection. This syndrome leads to low blood pressure and septic shock.

Q: What are the functions of pro- and anti-inflammatory responses?

Systemic inflammatory responses, including pro-inflammatory and anti-inflammatory responses, are stimulated when the body has undergone a bacterial infection. These responses create physiological changes worsening the patient’s condition.

Q: What are the three proteins produced by Anthrax germs?

Anthrax produces three types of exotoxin proteins in a patient’s body tissues. These proteins work together to enter the cell and destroy it. Once they enter the cells, the immune system triggers systemic inflammatory responses inducing confusion and coma.

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