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• War is the metaphor for inflammation. Both are necessary evils. Both are more-or-less stereotyped responses to outside threats. There are specialized troops (white cells), including suicide-commandos (neutrophils), long-term siege armies (granulomas), and many others. There are supply routes (vessels), communications and intelligence (mediators), and a huge array of lethal weapons (inflammatory enzymes). In war as in inflammation, there will be damage to both the enemy and to friendly forces, and there will very likely be severe damage to the battlefield itself. Despite idealistic rhetoric about "the laws of war", when the fighting starts, there is really only one law for the soldiers: "Kill your enemy." Like it or not, if you want peace, you must be prepared to fight under certain conditions. Like it or not, if you want to be healthy, your body must be able to mount an inflammatory response. Force will always rule our world. Our best hope is that this will be the force of good laws. And the best for which we can hope from the inflammatory response is that, for most of our lives, it will do us more good than harm.
• "Big Robbins" defines inflammation as "the reaction of vascularized living tissue to local injury". Inflammation is the name given to the more-or-less stereotyped ways our tissues respond to noxious stimuli, with blood vessels and white blood cells as its twin centerpieces and a host of proteins as actors. Inflammation "destroys, dilutes, or walls off the injurious agent" and sets in motion the limited powers of the body to heal itself. Inflammation and repair can and do themselves damage the body.
just like mosquito bites. at least unconsciously. tissue necrosis itself (except apoptosis). chemical or thermal burns.DIFFERENTIATION • Beginning medical students have a tendency to equate "inflammation" and infection. various poisons. . radiation injury.. yellow fever.) Noxious. plague and leprosy. and many of the opportunistic infections in AIDS are only three examples. non-infectious things that produce inflammation include trauma. and any of the four major types of immunologic injury. pimples. Several infectious diseases feature no inflammation (Creutzfeldt-Jacob disease. This is plain wrong.) A sunburn or a red scratch are inflammation.
blood vessels widen and disgorge protein. formerly a popular term used especially by surgeons for the patients who they could not save. with variable participation by lymphocytes. • Acute inflammation is almost completely stereotyped -over minutes to a few days.TYPES • Obviously. there are differences among inflammatory reactions. and neutrophils leave the bloodstream and rampage through surrounding tissues. and healing cells (fibroblasts and angioblasts). plasma cells. . • Chronic inflammation is more variable. • Whole body inflammation. is going out of fashion in favor of multiple organ failure. macrophages.
CARDINAL SIGNS • Cornelius Celsus (ancient Rome) described rubor (redness). Julius Cohnheim.this applies only to the skin). dolor (pain). and tumor (which then simply meant "swelling") as the "cardinal signs of inflammation • Rudolf Virchow added functio laesa (loss of function) as the fifth cardinal sign of inflammation. provided the basic studies of the pathologic microanatomy of inflammation . calor (heat -. and his student.
Lewis found that he could eliminate the flare.. This experiment led to the discovery of histamine.TRIPLE RESPONSE OF LEWIS • Someone may still ask you about the "triple response of Lewis" to a superficial scratch (after the momentary vasoconstriction): (1) a red scratch mark.e. (3) then a red swollen area ("wheal") around the flare. preventing the "axon reflex"). which mediates events 1 and 3. but not the others. (Try it!) Dr. (2) then a red flare around the scratch mark. . by cutting the autonomic nerve supply (i.
as anyone with a persistent pimple knows. • (2) entry of neutrophils into the tissues.HALLMARKS OF ACUTE INFLAMMATN • ACUTE INFLAMMATION: A stereotyped response to most kinds of noxious stimuli. . Something a part of the body does when it knows it's been hurt. This is a simplification. • Textbooks describe "acute inflammation" as lasting from moments to a maximum of 1-2 days. • The hallmarks of acute inflammation are • (1) vasodilatation and increased vascular permeability.
the arterioles dilate and stay dilated as long as acute inflammation continues. The slightly increased pressure that this causes in the capillaries may produce some transudation of fluid into the tissue spaces. . scratch yourself and see) up to a few minutes When the arteriolar constriction phase is over. lasting a few seconds (if at all. This produces the redness and (since heart's blood is warmer than exposed body parts) the sensation of heat.VASCULAR RESPONSE • The first event is transient arteriolar constriction.
This increases the osmotic ("oncotic") pressure of the interstitial fluid. Much of this fluid will return to the circulation only via the lymphatics. In the worst injuries (and. The physicochemical changes that cause the increased permeability to protein are only partly understood. they will leak. of course). or are themselves regenerating. of course. Of course. Another factor seems to be loss of various polyanions from the basement membrane surrounding the endothelial cells.• • • • • Hyperemia is a generic term for extra blood in an organ due to dilation of the arterioles. More about this soon. neutrophils stick to endothelium. The key seems to be opening gaps in the intercellular junctions ("endothelial cell contraction"). if the vessels are damaged by the first injury. The water that follows the protein out of the vessels contributes to edema. . and the viscous blood flows more slowly ("stasis"). or by the neutrophils. Red cells pack small vessels ("red cell stasis"). The worse the injury. the local concentration of cells in the blood increases. the larger the protein molecules that can pass through the vessel walls. water is drawn out of the vessels. if the vessel is severed). fibrinogen escapes into the tissue fluids. the small vessels (mostly the venules 20-60 microns) become permeable to some or all plasma proteins. and inflammatory edema ("swelling") results. Soon after injury. As protein leaks out into the interstitial spaces. and under these circumstances is certain to be transformed to fibrin (by your clotting cascade.
"segs". these predominate for the first 24-48 hours after injury. and are more or less replaced by macrophages after this time.e. (Most of the time. especially venules.. They roll along for a while. Adhesion to the walls of vessels.CELLULAR RESPONSE • The final key event in acute inflammation is the accumulation of neutrophils ("polys".) • The laws of physics cause neutrophils to marginate ("pavement". results when leukocyte adhesion molecules on the surface of the neutrophils interact with endothelial adhesion molecules on the endothelial cells. lie along the inner walls of vessels) whenever blood flow is slowed. nobody calls them * "microphages" nowadays) in the injured tissue. i. .
and monos). Various mediator proteins increase the numbers of some or all of these. diabetes. . • Alcoholism. and glucocorticoid therapy all reduce the numbers of adhesion molecules. You'll be impressed with the difficulty that such people have with fighting off bacteria.• Endothelial adhesion molecules include ELAM-1 (for neutrophils) and ICAM-1 (for neutrophils. lymphs.
) The other white cells also leave vessels by this route. then get through the basement membrane by digesting it with enzymes. but the endothelial cells repair the damage soon enough. complement components (remember C5a). . Most small molecules that are chemotactic for neutrophils are also chemotactic for macrophages and vice versa.• Emigration ("diapedesis") of neutrophils from the vessels into the tissues occurs when the cells squeeze through the widened endothelial cell gaps. • Various chemical mediators cause chemokinesis (increased random locomotion) and chemotaxis (directional migration) of neutrophils and other cells. (Of course this damages the blood vessels. Chemotactic agents include a plethora of bacterial breakdown products. and leukotriene B4.
(If only C3b is present in the opsonin.) Some of the lysosomal enzymes will leak out of the neutrophil and into the intercellular fluid. causing digestion within the phagolysosome. Killing of phagocytized bacteria is mediated through the H2O2myeloperoxidase-halide system . There are receptors for both on the neutrophil surface.• • • Once they have found their way to the tissues. They also degranulate. additional molecules will be required to trigger engulfment. The particle will then be engulfed and a lysosome membrane fused with the phagosome membrane. releasing enzymes into the interstitial fluid. Most particles must be coated (opsonized) by IgG (subtypes 1 or 3) or C3b. the neutrophils phagocytize things that shouldn't be there. Phagocytosis requires that the particle be recognized and attach to the neutrophil.
. and arachidonic acid metabolites are released during the process by "regurgitation during feeding". H2O2. such as a huge immune complex or a splinter. the neutrophil tries to eat something too big.• Neutrophil products. and "cytotoxic release . free radicals.e. including lysosomal enzymes. "frustrated phagocytosis" (i. it can't engulf it so it drools).
the lymphocytes are the principal cell. (3) In typhoid fever. (5) In clostridial gas gangrene. . the predominant cells are always the macrophages. there are few or no other cells besides the neutrophils. don't expect to see any white cells.EXCEPTIONS TO NEUTROPHILS • • • • • • • Notable exceptions to the "neutrophils first. monocytes later" rule: (1) In viral and rickettsial infections. eosinophils dominate from start to finish. (4) In most forms of acute dermatitis. (6) In many kinds of bacterial infections (including chlamydial ones). (2) In classic allergy and in some parasitic infections. lymphocytes are most abundant.
As proteases continue to work on the fluid itself. Healing by scarring 3.OUTCOMES OF AC INFLAMMATN • • • • Once acute inflammation has begun. 2. and only when.e. usually you still have to drain pus. Complete resolution. the neutrophils and their fast-acting molecular allies cannot remove the noxious agent • . causing it to swell ("ripen" -. This happens when. i. the osmotic pressure within the abscess becomes greater and greater. 4. there has been no damage to the connective tissue framework or non-recoverable cells of any part of the body. Pus in a confined space is called an "abscess".ever had a pimple?) While the body might succeed in walling it off.. Progression to chronic inflammation (). Abscess formation. there are four possible outcomes: 1.
it has specific gravity of extracellular fluid. i. (This is most common in the pleural cavities. A body fluid (either an exudate or an area of liquefaction necrosis) containing neutrophilic leukocytes and necrotic debris is pus. showing that it was white cells and necrosis • . protein-rich fluid that has leaked out of inflamed vessels. you need it drained by a surgeon. * Of course. The preferred adjective to describe things with lots of pus is purulent.e. it was Virchow who first demystified pus. Pus that literally fills an important body cavity is called an empyema.. 1. To produce pus is to suppurate.) If you've got a lot of pus. An exudate is an abnormal.ABNORMAL FLUIDS IN INTERSTITIUM • • • Terms for abnormal accumulations of fluid: A transudate is protein-poor salt water squeezed through blood vessels by hydrostatic pressure.010 or thereabouts.
but it is worth mentioning at this point that is not always the same color or thickness. hence the stronger yellow color. Classic yellow pus (as in a staphylococcal boil) also includes some lipid from necrotic tissue. • Clostridia produce extensive hydrolysis of tissue.PUS • Pus requires no description. pus is more yellow-gray. • Without necrosis (as in a streptococcal phlegmon). and the discharge from a clostridial wound contains free lipid and other small molecules that impart a "dirty dish-water" look. . • Pus always has a yellow-green tinge because of myeloperoxidase. • Pseudomonas bacteria make a pigment that imparts a bluegreen fluorescent sheen to pus.
calor (heat). tumor (swelling). and loss of function.CARDINAL SIGNS • The cardinal signs of inflammation are rubor (redness). compared to the more normal skin at the far right. . dolor (pain). Seen here is skin with erythema.
ACUTE CHOLECYSTITIS • The neutrophils are seen infiltrating the mucosa and submucosa of the gallbladder in this patient with acute cholecystitis and right upper quadrant abdominal pain with tenderness on palpation. .
. This abscess is an example of localized liquefactive necrosis.LIVER ABSCESS • The liver shows a small abscess here filled with many neutrophils.
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