idiopathic anaphylaxis information center

a resource for people with ia and other mast cell disorders

Anaphylaxis: What happens?

When we say that a person has anaphylaxis, what is happening inside his or her body?

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This is a worthwhile question to ask because if we can understand what is happening physiologically during anaphylaxis, it will make it much easier to decide when to administer an EpiPen, call 911 or take some other action.

Photograph of New York city ambulance; source: Wikimedia Commons

The first important thing to understand is that every single attack of anaphylaxis has the potential to be fatal. It doesn't matter if all of a person's previous attacks have been fairly mild or easily controlled with a "handful of Benadryl®." This is one case where previous history is not a reliable predictor of future events.

It is very important to treat each and every attack of anaphylaxis as though it is going to be "the big one." Doing anything less is playing an extremely dangerous game with the health and well-being of a human being. Anaphylaxis is always a medical emergency.

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Beauchamp kills Sharp, a lithograph; source: Wikimedia Commons

First, let's consider the case of a person who is attacked or in an accident and who develops a profusely bleeding wound. What is it that actually happens when a person "bleeds out"? Well, as the person loses blood, the circulatory system does what it can to attempt to make up for the reduction in the volume of circulating fluid. The heart may pump faster and harder, but as blood is lost, the body no longer has enough blood circulating to carry fresh oxygen and nutrients to cells, tissues and organs within the body. When the heart becomes empty of blood, the battle is lost. The heart is a fluid pump, and without fluid, all it can do is spasm uselessly. The person's body shuts down because his or her organs are starved for oxygen and nutrients and because there is no blood supply to help carry away toxins that build up.

Photograph of car crash in Copenhagen, Denmark; source: Wikimedia Commons

Next, consider the case of a person who has been injured and is said to be "bleeding internally." In this case, too, the circulatory system is losing blood, but the blood is not coming out of the person's body — instead it is pooling somewhere inside the person. It doesn't matter whether blood is lost inside or outside the body. Once it is no longer available to the circulatory system, it can no longer carry oxygen and nutrients to the organs that depend on circulation to remain viable. So a person can "bleed out" without ever having a drop of blood exit his or her body.

These analogies may help you understand what happens during anaphylaxis.

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Illustration of human circulatory system; source: Wikimedia Commons

The human circulatory system. Click on graphic to view at larger size. Use browser’s Back button to return.

When a person has an anaphylactic reaction, whether it is due to an allergic reaction or for some other reason, his or her mast cells and basophils release large amounts of histamine and other mediators. These biochemicals spread both locally and systemically, and wherever they go, they influence the cells and tissues within the body.

When most of us think of blood vessels — arteries and veins — we think of them like plastic tubing that routes the blood through our bodies. But of course, blood vessels are not plastic tubing. They are made up of living cells, and some of these cells react dramatically to the mediators that are released by mast cells and basophils during anaphylaxis.

These substances have two effects on blood vessels. First, they tend to make them relax and dilate, becoming bigger, "flabbier," their diameters increasing. This causes blood pressure to decrease.

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Second, histamine also causes the epithelial cells that line the blood vessels to shrink, becoming smaller, which creates perforations in the lining of the blood vessel. Just as a colander retains pasta but allows the water to drain, these "leaky" blood vessels allow plasma to escape while keeping the larger red blood cells inside. This can have the effect of reducing, dramatically, the amount of fluid available to the circulatory system.

Click the play button in the animation below to help you visualize how the endothelial cells lining blood vessels shrink when affected by histamine, and how this, in turn, creates gaps between the cells through which plasma can escape into the surrounding tissue, where it is lost from the circulatory system (please be patient — it can take time to load):

Once the plasma has escaped from the blood vessel into the surrounding tissues, there is no mechanism by which the blood vessels can quickly suck it back in. The plasma, once released, is gone until the lymphatic system is able to clean it up — hours or days later.

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Sign that says, 'Danger'

As the circulatory system loses more and more fluid, the heart fights to stabilize circulation. At first, the blood pressure can actually spike upward as the heart beats harder, but as the amount of fluid in circulation quickly decreases and the blood vessels become more relaxed and flaccid, the heart loses the battle and the blood pressure plummets.

Next, the body goes into shock, which means that the failing and insufficient blood supply is not able to meet the internal organs' need for foods, nutrients, and waste removal. All of the internal organs are affected by this crisis, although how quickly or how profoundly each one is affected is influenced by individual differences.

As my mother, a nurse, used to tell me, you can expect the weakest link in the chain to fail. A person who has, say, a weak heart, can expect that to be disproportionately affected by this process. It is not unusual for a person who has had serious anaphylaxis to have to spend days or weeks in the ICU, where they are treated for the aftereffects of the attack.

The biochemicals released by mast cells and basophils have more effects than just these, but when we're talking about anaphylaxis, these effects are the most important.

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Once anaphylaxis starts, the only sure way to halt or reverse it is by administering epinephrine, by autoinjector, syringe, and/or intravenous influsion (IV).

Illustration of EpiPen epinephrine autoinjectors

Epinephrine has the effect of making blood vessels contract (become less "flabby"), which helps to stabilize the blood pressure. Further, it has the ability to completely halt the degranulation of mast cells and basophils that is driving the anaphylaxis.

If the process has gone far enough to seriously reduce the amount of plasma in the circulatory system, the person having anaphylaxis will require IV administration of fluids — and perhaps other medications — to further stabilize circulation.

It is important to remember that an attack of anaphylaxis can be biphasic, which means that a second phase of the attack can occur within one to 72 hours of the orginal attack. A recent literature review noted that, "Failure to inject an adequate dose [of epinephrine] is reported to increase the risk of a biphasic reaction." Reference [Simons FER, Clark S, Camargo CA. Anaphylaxis in the community: Learning from the survivors. J Allergy Clin Immunol. 2009; 124:301–6]. The lesson here is that using an EpiPen promptly can reduce the likelihood that you'll have a second round of anaphylaxis soon after the first.

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It is also important to understand that H1 and H2 antihistamines, mast cells stabilizers, leukotriene inhibitors, and NSAIDs [Non-Steroidal Anti-Inflammatory Drugs] do not really stop anaphylaxis once it has begun.

These medications are useful in two ways: When taken on a regular basis, they can help make anaphylaxis less likely to occur, and they may also help clean up a portion of the mess that is made by an early stage or mild attack of anaphylaxis.

If taken very quickly, at the very first sign of an attack, H1 antihistamines can sometimes slow it down long enough for the person to get away from the allergen or trigger or to self-administer epinephrine by autoinjector.

If the attack is extremely mild, sometimes those antihistamines can be enough to head it off. However, the problem is that just because an attack seems mild at first, that doesn't mean that it won't escalate rapidly out of control.

Even if a person has a history of very mild attacks, that does not mean that the next one won't be lethal.

For further information, you might want to check out other articles on this site, such as But is it anaphylaxis? and Third-spacing.

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Page last updated: May 31, 2011

All information contained in this site is one layperson's interpretation of medical journal articles, textbooks, seminars, presentations, and other materials. Nothing that is stated here should carry more weight than the informed and considered opinions of your own highly trained and qualified medical caregivers. The author of this site is not a doctor and has absolutely no authority to prescribe or diagnose.

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