Acute inflammation is the term used for early stage inflammatory responses. Acute inflammation is characterized by rapid appearance of the five cardinal signs: heat, swelling, pain, redness, and loss of function.

The most immediate of the signs are pain and redness. Swelling and heat also begin rapidly and may become quite impressive, depending on how vigorous the inflammatory response becomes. Loss of function is typically a sign that appears more gradually, but this is not always the case.

Early events in acute inflammation include edema, hyperremia, and infiltration of the affected tissue by large quantities of neutrophils. The identifying hallmark of the acute response is a rapidly growing neutrophilia in response to insult or injury.

Events such as increased blood flow (hyperremia) and increased permeability of the vasculature are in fact designed to bring neutrophils to the affected site as rapidly as possible. Neutrophils are vitally important as they are responsible for the cytokines that perpetuate the inflammatory response, prime the immune system, and summon more granulocytes. Neutrophils leave the circulation and arrive at the site of injury, attracted there by an elaborate series of molecular messengers and cytokines: they follow the chemical gradient of these substances to the right location in the bloodstream. Once in the right neighborhood they follow a characteristic pattern of margination in the blood vessels, rolling along the endothelium to the affected site, adhesion to the endothelium, and extravasation into the interstitium. Inflammation is a connective tissue phenomenon: the cells have to exit the blood and enter the CT space for it to take place.

Adhesion is a most important step, allowing the neutrophils to make their way to the site of injury. Adhesion is controlled by a delicate interplay of selectins, integrins, and immunoglobulins.

Extravasation and transmigration into the interstitium give neutrophils access to their targets. Neutrophils are one-shot cells: after they phagocytize a bacterium, they kill it with a burst of oxidative activity, and soon afterwards die. Neutrophils also secrete certain cytokines that sustain the inflammatory response and summon macrophages.

It's important to recognize that inflammation is not, in and of itself, a bad thing. Inflammation is part of the mechanism of healing, and without it no healing would occur at all. The initial events are designed in part to lead to a continued response, with different cell types playing different roles as the response progresses. If for some reason the inflammatory response doesn't run its course and die out, as it's supposed to do, then the situation tips over into a condition of chronic inflammation.


This is a section through the external ear of a laboratory rabbit, used here as an example to demonstrate the process of acute inflammation. The pink line down the middle is the elastic cartilage of the pinna; on either side is the CT and overlying epidermis.

A small amount of an irritant chemical (turpentine) was applied to one side of the ear, and sections made to show the progression of the inflammatory response. You'll notice that one one side of the pinna the subcutaneous CT is somewhat enlarged compared to the other: that's the site of the treatment.

This image was taken about six hours after treatment. The normal side is on the bottom, the affected side on the top. From this magnification, the increased degree of tissue edema , mild hyperemia, and inflammatory exudate should be apparent on the lower side in comparison to the upper.


This image and the one to the right clarify the differences between the inflamed and non-inflamed sides. One side is more or less normal: the epidermis is intact, there is no separation of the fibers of the dermis, and there is no loosening of the CT of the perichondrium. The treated side shows loosened dermal CT caused by the rlease of fluid from the very congested blood vessels. This transudation of the liquid phase of blood is the result of increased flow and increased permeability of the vessels: the term for it is edema. The fluid forces its way into the interfibrillar spaces of the CT, and has even begun to loosen the perichondrium. The blood vessels are congested and hyperremic because of the unsuaully large amount of blood coming into the area. The increased flow of blood brings heat and the release of fluid causes the swelling associated with inflammation. Some inflammatory cells have arrived, but not many, since the inflammation is still in an early stage. These will be neutrophils and a few macrophages.

Here's a close up image of a couple of neutrophils that have undergone margination and have adhered to the wall of the congested blood vessel. They've found the place they want to exit, and will shortly undertake diapedesis, slithering through the loosened joints between the capillary endothelial cells. You can see this happening in the image below at left.

Diapedesis is a fairly common phenomenon, especially among the white blood cells, which aren't truly "blood" cells at all, since their real function is in the CT spaces. Not just neutrophils do it: the monocytes that exit the vascular system complete their differentiation into resident macrophages, lymphocytes will exit to deal with infectious agents or in response to cytokines that require their presence to deal with cell mediated reactions, and eosinophils will exit when an allergic reaction is in progress. These activities involve intracellular microtubules and amemboid movement by the cells after they leave the blood.

After 40 hours you can see that there has been considerable change, and that the condition has worsened. The inflamed section at the top of the field not only shows more edema, and congestion, it has developed a necrotic region where cells have died as a result of exposure to the toxin. Necrotic tissue is in and of itself a powerful inflammatory stimulus, so if something doesn't happen this may snowball into an ongoing and non-healing lesion.

The inflammatory infiltrate has progressed beyond just of neutrophils; it's entered the exudative stage and while neutrophils are present in large numbers, macrophages are beginning to show up, too, summoned by the necrotic material and the chemical signals it sends out. Macrophages have the job of cleaning up the battlefield, so to speak: they migrate in and begin engulfing debris of lysed cells and also the bodies of the dead neutrophils that have been used up. The vascular dilation now includes smaller venules as well as larger veins. In the image at right you see the infiltrate and some of the edematous regions. The edema is not as diffuse as it was earlier: it's slowly becoming organized.

It's possible to judge the state and duration of an inflammation response by the cells present and the degree to which tissue destruction has taken place. In this image a good many neutrophils (N) are still present, but macrophages (M) are beginning to arrive in fairly large numbers.

Immature macrophages are small and mononuclear; they may be quite eosinophilic, but with time they get larger and stain more palely, as their content of lysosomal enzymes increases. The viable neutrophils are easily told by their multi-lobulated nuclei. Remember that white blood cells look somewhat different in tissue sections compared to smears; and that there is a continuum between the just-arrived-and-not-yet-fully-differentiated macrophage and those that have been on the job for a while. You can expect to see many intermediate stages, because transition from one state to the other isn't a quantum jump.

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