Part 2 SIRS-Systemic Inflammatory Response Syndrome Cascade/Sepsis (how it spreads).

 

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It is the body’s response to an infectious or noninfectious insult. Although the definition of Systemic Inflammatory Response Syndrome (SIRS) refers to it as an “inflammatory” response, it actually has pro- and anti-inflammatory components.  SIRS is a serious condition related to systemic inflammation, organ dysfunction, and organ failure. It is a subset of cytokine storm, in which there is abnormal regulation of various cytokines.   Cytokines are this, the term “cytokine” is derived from a combination of two Greek words – “cyto” meaning cell and “kinos” meaning movement. Cytokines are cell messaging or signaling molecules that aid cell to cell communication in immune responses and stimulate the movement of cells towards sites of inflammation, infection and trauma.

Cytokines exist in peptide, protein and glycoprotein (proteins with a sugar attached) forms. The cytokines are a large family of molecules that are classified in various different ways due to an absence of a unified classification system.  Protein is acidic as opposed to being alkalinic.

Examples of cytokines include the agents interleukin and the interferon which are involved in regulating the immune system’s response to inflammation and infection.

SIRS, independent of the etiology/cause, has the same pathophysiologic properties, with minor differences in inciting cascades. Many consider the syndrome a self-defense mechanism. Inflammation is the body’s response to nonspecific insults that arise from chemical, traumatic, or infectious stimuli. The inflammatory cascade is a complex process that involves humoral and cellular responses, complement, and cytokine cascades.  Best summarized in the relationship between these complex interactions and SIRS is it is in the following 3-stage process.  Here is a simple explanation in what occurs without taking pages in explaining the stages to you.

Stage I

Following an insult to the body, cytokines are produced at the site. Local cytokine production incites an inflammatory response, thereby promoting wound repair and recruitment of the reticular endothelial system. This process is essential for normal host defense homeostasis and if absent is not compatible with life. Local inflammation, such as in the skin and subcutaneous soft tissues occurs.

What occurs is rubor or redness at the site that reflects local vasodilation of vessels.  What is caused by release of local vasodilation of the vessels at the area of where the insult starts in the body is substances like nitric oxide (NO) and prostacyclin get released=Acidic.

Tumor or swelling occurs due to vascular endothelial (layer of the skin) tight junction disruption and the local extravasation of protein-rich fluid into the interstitium (layer of the skin), which also allows activated white blood cells to pass from the vascular space (blood stream) into the tissue space to help clear infection and promote repair.

Dolor is pain and represents the impact inflammatory mediators have on local somatosensory nerves. Presumably, this pain stops the host from trying to use this part of his or her body as it tries to repair itself.

The increased heat primarily due to increased blood flow occurs but also increased local metabolism as white blood cells become activated and localize to the injured tissue.

Finally, the loss of function, a hallmark of inflammation and a common clinical finding of organ dysfunction with the infection is isolated to a specific organ (ex. pneumonia—acute respiratory failure; kidney—acute kidney injury. pancreatitis–  inflammation of the pancreas).

Importantly, on a local level, this cytokine and chemokine release by attracting activated leukocytes to the region may cause local tissue destruction (ex. abscess) or cellular injury (ex. pus), which appear to be the necessary byproducts of an effective local inflammatory response.  Local infection signs & symptoms= puss, swelling. skin temperature  hot, pain and redness to the where the insult of the body is.

Ending line what happens is an insult occurs in the body, there is local cytokine production with the goal of inciting an inflammatory response thereby promoting wound repair and recruitment of the reticular endothelial system.  Your body is compensating in reacting normally to this insult.

Stage II

Small quantities of local cytokines are released into the circulation, improving the local response. This leads to growth factor stimulation and the recruitment of macrophages and platelets. This acute phase response is typically well controlled by a decrease in the pro-inflammatory mediators and by the release of endogenous antagonists; the goal is homeostasis. At this stage, some minimal malaise (general weakness)and low-grade fever may become show.

Putting it simple what occurs here is small quantities of local cytokines are released into circulation to improve the local response. This leads to growth factor stimulation and the recruitment of macrophages (cells eating up toxins to the body) and platelets (that are cells the coagulate-cause clotting). This acute phase response is typically well controlled by a decrease in the proinflammatory mediators and by the release of endogenous antagonists. The goal is homeostasis – the body still trying to compensate and react productively to this insult to the body.

Stage III

If homeostasis is not restored and if the inflammatory stimuli continue to seed into the systemic circulation, a significant systemic reaction occurs. The cytokine release (acidic) leads to destruction rather than protection. A consequence of this is the activation of numerous humoral cascades and the activation of the reticular endothelial system and subsequent loss of circulatory integrity.  The body at this stage is decompensating and not productively fighting off this insult to the body and this leads to end-organ dysfunction.

Tune in tomorrow to part 3 of SIRS the conclusion of this topic (extensive noninfectious and infectious causes with more on coagulation and multi cascading reactions in the body due to SIRS).

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