“SIRS can be incited by ischemia, inflammation, trauma, infection or a combination of several “insults”. SIRS is not always associated with infection. While not universally accepted, some have proposed the terms “severe SIRS” and “SIRS shock” to describe serious clinical syndromes that are not infectious in nature and thus cannot be labeled according to the various sepsis definitions”

Steven D. Burdette M.D. (Infectious Disease Medicine M.D.– Wright State Physicians in Dayton, Ohio – http://www.healthgrades.com/physician/dr-steven-burdette-yhfgy)

Part 3 talks to you about the multi-hit theory of SIRS with Inflammatory Cascade of SIRS and lastly the coagulation process in SIRS.   It also informs you of infectious and non-infections of SIRS.

Multi-hit theory

A multi hit theory behind the progression of SIRS to organ dysfunction and possibly multiple organ dysfunction syndrome (MODS). In this theory, the event that initiates the SIRS cascade primes the pump. With each additional event, an altered or exaggerated response occurs, leading to progressive illness. The key to preventing the multiple hits is adequate identification of the ETIOLOGY or CAUSE of SIRS and appropriate resuscitation and therapy.

Inflammatory cascade

Trauma, inflammation, or infection leads to the activation of the inflammatory cascade. Initially, a pro-inflammatory activation occurs, but almost immediately thereafter a reactive suppressing anti-inflammatory response occurs. This SIRS usually manifests itself as increased systemic expression of both pro-inflammatory and anti-inflammatory species. When SIRS is mediated by an infectious insult, the inflammatory cascade is often initiated by endotoxin or exotoxin. Tissue macrophages, monocytes, mast cells, platelets, and endothelial cells are able to produce a multitude of cytokines. The cytokines tissue necrosis factor–alpha (TNF-α) and interleukin-1 (IL-1) are released first and initiate several cascades.

The release of certain factors without getting into medical specific terms they ending line induces the production of other pro-inflammatory cytokines, worsening the condition.

Some of these factors are the primary pro-inflammatory mediators. In research it suggests that glucocorticoids may function by inhibiting certain factors that have been shown to be released in large quantities within 1 hour of an insult and have both local and systemic effects. In studies they have shown that certain cytokines given individually produce no significant hemodynamic response but that they cause severe lung injury and hypotension. Others responsible for fever and the release of stress hormones (norepinephrine, vasopressin, activation of the renin-angiotensin-aldosterone system).

Other cytokines, stimulate the release of acute-phase reactants such as C-reactive protein (CRP) and pro-calcitonin.

The pro-inflammatory interleukins either function directly on tissue or work via secondary mediators to activate the coagulation cascade and the complement cascade and the release of nitric oxide, platelet-activating factor, prostaglandins, and leukotrienes.

High mobility group box 1 (HMGB1) is a protein present in the cytoplasm and nuclei in a majority of cell types. In response to infection or injury, as is seen with SIRS, HMGB1 is secreted by innate immune cells and/or released passively by damaged cells. Thus, elevated serum and tissue levels of HMGB1 would result from many of the causes of SIRS.

HMGB1 acts as a potent pro-inflammatory cytokine and is involved in delayed endotoxin lethality and sepsis.

Numerous pro-inflammatory polypeptides are found within the complement cascade. It is thought they are felt to contribute directly to the release of additional cytokines and to cause vasodilatation and increasing vascular permeability. Prostaglandins and leukotrienes incite endothelial damage, leading to multi-organ failure.

Polymorphonuclear cells (PMNs) from critically ill patients with SIRS have been shown to be more resistant to activation than PMNs from healthy donors, but, when stimulated, demonstrate an exaggerated microbicidal response (agents that kill microbes). This may represent an auto-protective mechanism in which the PMNs in the already inflamed host may avoid excessive inflammation, thus reducing the risk of further host cell injury and death.

Coagulation

The correlation between inflammation and coagulation is critical to understanding the potential progression of SIRS. IL-1 and TNF-α directly affect endothelial surfaces, leading to the expression of tissue factor. Tissue factor initiates the production of thrombin, thereby promoting coagulation, and is a pro-inflammatory mediator itself. Fibrinolysis is impaired by IL-1 and TNF-α via production of plasminogen activator inhibitor-1. Pro-inflammatory cytokines also disrupt the naturally occurring anti-inflammatory mediators anti-thrombin and activated protein-C (APC).

If unchecked, this coagulation cascade leads to complications of micro-vascular thrombosis, including organ dysfunction. The complement system also plays a role in the coagulation cascade. Infection-related pro-coagulant activity is generally more severe than that produced by trauma.

What the causes of SIRS can be:

The etiology of systemic inflammatory response syndrome (SIRS) is broad and includes infectious and noninfectious conditions, surgical procedures, trauma, medications, and therapies.

The following is partial list of the infectious causes of SIRS:

• Bacterial sepsis
• Burn wound infections
• Candidiasis
• Cellulitis
• Cholecystitis
• Community-acquired pneumonia ^[5]
• Diabetic foot infection
• Erysipelas
• Infective endocarditis
• Influenza
• Intra-abdominal infections (eg, diverticulitis, appendicitis)
• Gas gangrene
• Meningitis
• Nosocomial pneumonia
• Pseudomembranous colitis
• Pyelonephritis
• Septic arthritis
• Toxic shock syndrome
• Urinary tract infections (male and female)

The following is a partial list of the noninfectious causes of SIRS:

• Acute mesenteric ischemia
• Adrenal insufficiency
• Autoimmune disorders
• Burns
• Chemical aspiration
• Cirrhosis
• Cutaneous vasculitis
• Dehydration
• Drug reaction
• Electrical injuries
• Erythema multiform
• Hemorrhagic shock
• Hematologic malignancy
• Intestinal perforation
• Medication side effect (ex. from theophylline)
• Myocardial infarction
• Pancreatitis
• Seizure
• Substance abuse – Stimulants such as cocaine and amphetamines
• Surgical procedures
• Toxic epidermal necrolysis
• Transfusion reactions
• Upper gastrointestinal bleeding
• Vasculitis

PREVENTION IS THE KEY!   So stay healthy and out of  hospitals!*

The treatment is don’t get it since it is hard to get rid of especially the people over 65 and in hospitals.  There is no one Rx for it.  If your unfortunate enough to be diagnosed with SIRS the sooner you get diagnosed with it including being in stage one as opposed to three the better the turn out will be for you.  Again the key is prevention; don’t get it.

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.

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).

“Current theories about the onset and progression of sepsis and SIRS focus on dysregulation of the inflammatory response, including the possibility that a massive and uncontrolled release of proinflammatory mediators initiates a chain of events that lead to widespread tissue injury.”

Dr. Remi Neviere, MD/Professor/Author of Sepsis and the systemic inflammatory response syndrome: Definitions, epidemiology, and prognosis  http://www.uptodate.com/contents/sepsis-and-the-systemic-inflammatory-response-syndrome-definitions-epidemiology-and-prognosis & http://circ.ahajournals.org/content/111/20/2596

MD Department of Physiology, Univ. Droit et Sante – Lille II

“If you regularly experience a rapid or irregular heartbeat, you may be experiencing atrial fibrillation. Atrial fibrillation is a condition that occurs when the upper chambers of your heart receive irregular electrical signals. The chamber responds by quivering, which in turn overloads the AV node between the atria and the ventricles. The result is the irregular heartbeat called atrial fibrillation.”

alot.com “Understanding Atrial Fibrillation”

After reviewing the anatomy and physiology of the human heart and seeing how it functions with the lungs, and blood for carrying oxygen and dispensing carbon dioxide from other areas of the human body to ending spot the lungs in exhaling, now lets learn how cardiac disease effects the heart to function in doing this process.  Today lets talk about atrial fibrillation and Rapid Ventricular Rate/Response.

Some people in the US have this cardiac condition called Atrial Fibrillation where some with this condition even experience Rapid Ventricular Rate or Response with it.

Atrial fibrillation is an irregular and often rapid heart rate that commonly causes poor blood flow to the body.

During atrial fibrillation, the heart’s two upper chambers (the atria) beat chaotically and irregularly — out of coordination with the two lower chambers (the ventricles) of the heart causing your pulse to be irregular. We know now how the blood flows through the heart but due to the irregularity of the atriums which is not allowing the chambers to fill up to the maximal level they normally did when they didn’t have Atrial Fibrillation is decreasing the cardiac output (blood volume) from the left ventricle to be decreased.   This means the heart and all other tissus aren’t getting the regular amount of oxygen they got when they were in a regular normal rhythm.  Atrial fibrillation symptoms often include heart palpitations, shortness of breath and weakness.  Atrial fibrillation (also called AFib or AF) is a quivering or irregular heartbeat (arrhythmia) that can lead to blood clots, stroke, heart failure and other heart-related complications. Some people refer to AF as a quivering heart.  What happens here is primarily the ventricles take over.   With the atriums quivering and the ventricles going at their rate this causes an irregular heart rate HR.  Another problem with an irregular heart rate is this allows blood to pool in the heart putting the patient at risk for clot formation.  As this HR gets more irregular it puts the patient at a higher risk of allowing the clot to break off inside the heart now flowing freely in the blood stream.  If it reaches the lungs and stays there a pulmonary thrombus can occur causing breathing difficulties; if it bypasses the lungs the next place it goes to is the brain putting the person at risk for a stroke and if it reaches back to the heart the patient can have a heart attack.  This why you commonly see patients with atrial fibrillation on the med Coumadin or some form of anticoagulant drug to prevent clots from occurring.

An estimated 2.7 million Americans are living with Afib.

Episodes of atrial fibrillation can come and go, or you may develop atrial fibrillation that doesn’t go away and may require treatment. Although atrial fibrillation itself usually isn’t life-threatening, it is a serious medical condition that sometimes requires emergency treatment. It can lead to complications. Atrial fibrillation may lead to blood clots forming in the heart that may circulate to other organs and lead to blocked blood flow (ischemia) to even stroke/heart attack to pulmonary thrombus as stated earlier.

Treatments for atrial fibrillation may include medications like anticoagulants primarily=usually Coumadin,  antiplatelets= aspirin (platelets are responsible for clotting in our bloodstream) with and other interventions to try to alter the heart’s electrical system such as cardioversion-shocking the heart at low level voltage, more common in newly diagnosed afib. in hope to knock the afib into a regular rhythm called normal sinus rhythm (the best rhythm to be in).

Various studies have reported that electrical cardioversion is over 90 percent effective in converting to a normal sinus rhythm though many people revert back into afib shortly thereafter. Success has been shown to be enhanced when patients are on an antiarrhythmic drug beforehand, which helps prevent reverting back to atrial fibrillation.

Success depends on the size of the left atrium as well as how long the patient has been in afib. Patients with a very large left atrium, one greater than 5 cm, or who have been in constant afib for a year or two, may find that electrical cardioversion is not effective in converting to or maintaining a normal sinus rhythm.

Following a successful electrical cardioversion, the goal is to maintain a normal sinus rhythm, which only happens with about 20–30 percent of patients within the first year if they are not on antiarrhythmic drugs for rhythm control. Overall, the likelihood is quite high that you will revert back into atrial fibrillation, regardless of whether you stay on rhythm control drugs.

When the ventricles beat too rapidly they don’t fill completely with blood from the atria. As a result, they cannot efficiently pump blood out to meet the needs of the body. This can ultimately lead to heart failure in time if not treated.  Just like us running from NY to California most will end up not being able to do it just like the heart can’t run in atrial fibrillation in a high heart rate for a long time,  it also will give out going into failure.  The heart can only compensate in atrial fibrillation in a rapid high heart rate for so long.

A cardiac condition called Rapid Ventricular Rate or Response which is seen sometimes with Atrial Fibrillation which is the heart is overloaded.  Our heart beats lub dub which is first the atriums opening and closing (lub) and than the ventricles opening and closing (dub).  When the heart gets overworked and tries to compensate the atriums can give up and just allow the ventricles to take over to beat which affects the heart and all other tissues to get proper amount of blood with oxygen in time.  Since you loose the atriums (the upper chambers of the heart) and they don’t fill up with the amount of blood volume like they use to.  You loose a lot of blood volume(RBC’s); what the heart pumps out in the left ventricle to our tissues with oxygen get’s decreased in what we call your cardiac output=the volume of oxygenated blood pumped out of the left ventricle.  Well with atrial fibrillation this gets compensated.  In time if this is not repaired the blood goes backwards in how the heart pumps the blood.  It is regurgitating blood back in the heart back in the pulmonary vein back to the lungs putting fluid in the lungs even going further back into the Rt side of the heart and the superior vena cava and even further depending how long this hasn’t been treated.  Heart failure is set up, if not already.

Heart failure as a result of Atrial Fibrillation with RVR is most common in those who already have another type of heart disease like CAD (Coronary Heart Disease, CHF, etc…).

RVR can cause chest pains and make conditions like congestive heart failure worse.   RVR is simply having a high heart rate with the ventricles only pumping.  The HR can be like 140 or 160.  You need to get to an ER to be treated immediately.  This is where you would be started on a IV drip like Cardizem to bring the HR down to get you in controlled atrial fibrillation or some type of medication in bringing the HR down.  HR meaning the heart rate.

There are 2 types of atrial fibrillations controlled and uncontrolled.  If you are seen every 6 months or sooner with atrial fibrillation keeping your pulse under 100, which is controlled atrial fibrillation that is effective in treating it.

If you are with a pulse over 100 your in Uncontrolled Atrial Fibrillation and need your cardiologist to evaluate what needs to be done to bring the pulse under 100 so that it is less stressful for your heart to beat.  Than would be ideal under 100 as opposed to over 100.  It your over 100 higher odds you could go into RVR or just another rhythm more complicated than atrial fibrillation.  The more stressed out your heart is in doing its function the higher the odds your heart will go into problems.  So keep the pulse under 100 if you have afib and if not get checked out by your cardiologist or any doctor now not 2 mths or 2 weeks from now.

Always check with your doctor when you question anything medical about your self but at any time if you feel chest pain, chest discomfort, headache, palpatations, dizziness, shortness of breath or difficulty breathing call your doctor and be resting in hopes that the symptoms decrease to disappear.

If you have chronic atrial fibrillation you can live a completely normal life only with keeping the pulse under 100 and following up with your cardiologist as he/she orders.

“Giving up smoking is the easiest thing in the world. I know because I have done it a thousand times.”

Mark Twain

“Anything that raises your heart rate and gets your blood pumping is a workout for your heart and circulatory system,” .

Stuart Amory personal trainer

According to the Stroke Association, walking briskly for up to 30 minutes can help prevent and control the high blood pressure that can cause strokes – reducing your risk by up to 27 per cent.

American Stroke Association

First diet doesn’t necessarily mean you’re on a struggle eating special foods. Diet can simply mean that the foods that your eating and if done regularly eating foods HIGH in FAT, CHO (carbohydrates), CALORIES, and SUGAR you will also be high in your weight count unless you are working out extensively since it allows you to burn off the excess in FAT, CHO, CALORIES and SUGAR that the body doesn’t need. What also plays a role is your activity and this does not include your regular activities of daily living (so work doesn’t count even if you are in a job constantly on your feet, like possibly a Doctor, a traffic controller, or even a Nurse, like myself for over 27 years, in hospital settings…).   So some form of exercise, not having to be aerobic but if you do more power to you, it has to be done daily or every 2 to 3 times a day. Why and how does this help the body?

Is there anyone out there like myself that had nice legs but in time became bigger where you went from having 2 tone frankfurter legs ( nice and juicy) to 2 fat sausages looking well done (cellulite kicking in) causing you to cover them up with only fitting into dark leggings. Well I resolved this problem and it didn’t take vigorous working out either. It took discipline with the understanding of how the body works in creating pounds of additional fat/cellulite on the body due to diet and not doing routine or any exercise. My arms, abdomen, face with the neck (to some degree) started looking better through my diet change.   I increased my metabolism and kept it at a steady rate=6 small low glycemic meals a day which takes into account the amount of fats, CHOs, sugars, calories and small HIGH PROTEIN meal sizes that you eat.   The ending result when eating high glycemic meals and even large portion low glycemic meals causes fat storage in the body=cellulite, which we see in time. This is due to meals that are too high in calories, fat, sugars, CHO’s. Most adult Americans are overweight (over 60%) this is because many eat more than what the body needs for energy at that one time. After the energy that is needed by the body at that time is used from that meal then the extra energy=free circulating glucose in the bloodstream gets stored somewhere in the body causing an increase in fat storage on the body=Increase in the body weight.   Keep in mind ladies after 40 y/o pre and actual menopause occurs at sometime. This causes the metabolism to slow down even more which in turn causes an increase in the chance of putting weight on at the abdomen, legs, & hips. Our fuel for the body is FOOD&one of the ending products making up our fuel is glucose & when used in excess=a large meal, you store a lot of glucose away=fat storage=Wt. gain.   For further info go to my web page. 1

Another key in keeping healthy and even toning up muscles, especially in the legs is WALKING. This activity helps the body in 2 major ways (without doing major work-outs). One it helps the human body in both toning it (particularly the legs) and losing weight. Than 2 it helps prevent certain diseases, especially if you are still young adolescence or a young adult aged without disease at this time .

What physical activity does (even just walking briskly for 1-2 miles a day or 2-3x a week on a routine basis) will help in weight and health. Other than regular activities of daily living, like walking, burns calories, increases your good cholesterol (HDL) and decreases your unhealthy triglycerides. This helps prevent certain cardiac diseases; like blockages in the arteries=arthrosclerosis or strokes due to blockages or even helping someone already diagnosed with it by maintaining it with other RX methods (Ex. Meds, diet, etc…). Walking and even jogging improve circulation in the legs, and proper circulation helps ward off the development of varicose veins. Exercise also reduces overall high blood pressure and strengthens your entire circulatory system. The higher in the intensity of the activity the higher in number of calories you burn which includes CHO’s.   Activity/Exercise causes your metabolism to increase giving you an extra boost of energy (can even boost up the sex life, you have that extra energy) I have even increased my activity outside at home using the pool and walking with my sweetheart & dogs on our 2+ acres which makes a nice walk for all. It has proven to me that it has improved my sleep from doing the activity at least 4 to 6 hours, if not earlier, before sleeping, since it does increase your metabolism causing you to be more awake at first. Activity in your life can only benefit you, Remember to check with your general practitioner before starting any new exercise program, especially if you have any health concerns/diseases.  If you want to learn more about how to diet with exercise (not necessarily intense workout) and make yourself healthier with even getting others involved to do the same than join me at my website healthyusa.tsfl.com and read the information it provides and see if this is something you would want. No fee, no charge, no donations or hacking. I hope you join me; if I can do it, you can do it. All it takes is a little drive in wanting to feel and even look better for yourself and others being a good mentor (for children, spouse, family, and friends, etc…) to spread healthiness in the USA.   It would benefit everyone (even our healthcare) in time=less disease/illness for the next era and even generation to come. Thank you for your reading striveforgoodhealth.com.