By Ruth Werner
Originally published in Massage & Bodywork magazine, February/March 2007.
“Probably your own death will be caused by your last inflammatory response.”1
—Ed Friedlander, Pathguy.com
Ever since I came on board Massage & Bodywork, I have used this column to discuss pathology for massage therapists. I have introduced ideas about cortisol secretion, sleep deprivation, and what happens when pregnancy overlays autoimmune disease. In this issue, I will take on one of the most complex, aggressive, protective, and potentially dangerous of all natural processes—inflammation.
In this article, we will review some key concepts of inflammation, compare acute to chronic states, enumerate all the possible outcomes of an inflammatory response, and look at how recent discoveries reveal that some of the most common non-infectious diseases we face turn out to be related in part to the inflammatory process.
While this information may feel technical and arcane, massage therapists—like it or not—are increasingly regarded as healthcare professionals. It is our responsibility to track current trends in the medical field, especially when they affect the people we serve. And who among us has no clients with heart disease, diabetes, cancer, depression, or the threat of Alzheimer’s? For their benefit, and our own, we need to remain current on these important topics.
The inflammatory process is a response to tissue injury and/or the threat of infection. Infection is not synonymous with inflammation. It is possible to have injury without pathogenic invasion (think of a sprained ankle), and some of the most dangerous infections don’t trigger a substantial inflammatory response (Creutzfeldt-Jakob disease, the human variant of mad cow, for example).
The key features of inflammation—rubor, calor, dolor, tumor, and functio laesa (redness, heat, pain, swelling, and loss of function)—have been noted since the earliest days of medicine. The mechanisms behind these processes are extremely complicated, and our understanding of them expands daily.
Inflammation is brought about by a combination of overlapping responses from blood vessels, nerve endings, mobile and stationary cells, and a wide variety of chemicals from nearby cells and plasma. It ranges in severity, although severity is not always strictly tied to timing. Inflammation is often discussed as an acute, subacute, or chronic situation.
Acute inflammation is the immediate response to injury or invasion. It typically begins with vasoconstriction, followed by vasodilation. (You can demonstrate this on yourself by scratching your skin with a fingernail. A white wheal appears, soon to be followed by a reddish streak—acute inflammation in action, even without substantial tissue damage.)
If cells, especially endothelial cells from tiny capillaries, are damaged, they leak chemicals that reinforce the acute inflammatory response. Histamine, serotonin, and prostaglandins all support local vasodilation (along with osmosis to draw fluid from capillaries) and increased membrane permeability. Other chemicals trigger the cascade of events that leads to the weaving of fibrin and clot formation. Nearby platelets, normally smooth and flexible, are activated and suddenly grow sticky spikes to adhere to damaged blood vessel walls. (This process reminds me of the agitated puffer fish in Finding Nemo).
Varieties of white blood cells (WBCs) arrive with platelets. While neutrophils are usually the first on the scene, different infectious agents may call up other types of leukocytes. The WBCs kill off any local pathogens they can find and begin the process of forming tissue exudate—this can be the fluid that accumulates in uninfected blisters, or it can be a polite word for pus, which is essentially a collection of dead WBCs and liquefied necrotic tissue.
The length of the acute phase of inflammation varies with the severity of the infection or injury. A scraped knuckle may be swollen and irritated for only a few hours, while a badly sprained ankle may be throbbing and painful for two days or more.
Subacute Inflammation and the Maturation Stage
The main purpose of the acute phase of inflammation is to limit the spread of potential infection and to prepare the area for the best quality of recovery possible. When only quickly replaceable epithelial cells have been damaged, this can be accomplished without the production of scar tissue. But when damage affects multiple layers of tissues, fibroblasts must be recruited to manufacture the material that literally knits us back together—the collagen that forms scar tissue.
The subacute and maturation stages of the inflammatory process are fascinating and pertinent for massage therapists, particularly as they apply to orthopedic structures—muscles, tendons, ligaments, and tenosynovial sheaths. These stages determine how scar tissue is formed, and its orientation determines the long-term quality and strength of the healed structures. However, they are not the focus of this discussion. (For more information on these fascinating processes, please consult the notes and resource at the end of this article.)
Occasionally, the inflammatory process is not wholly successful. Pathogens or irritants are not removed from the body, or the immune system continually attacks some type of tissue as though it were a pathogen, as seen with autoimmune diseases. Under these circumstances, two well-recognized consequences may arise: abscesses or excessive scar tissue (or both).
Abscesses are isolated pockets of infectious material. They are frequently lined with granulomas—clusters of macrophages that work to build a “wall” between the perceived pathogen and the rest of the body. Abscesses are associated with long-term bacterial infections, which may be dangerous or benign. A deep “cystic” pimple is an example of an abscess that is eventually reabsorbed, leaving a connective tissue pocket behind. When an abscess grows around a tooth, it’s time for a root canal.
Alternatively, the affected area can be infiltrated with WBCs and fibroblasts that spit out massive amounts of collagen fibers. An excessive accumulation of scar tissue can interfere with organ function. This happens when deposits of scar tissue clog up the liver in cirrhosis or scar tissue blocks the digestive tract or other passageways.
When scar tissue obstructs a passageway, the body has a remarkable adaptation. It attempts to build new tubes into other hollow areas or to the skin. These fistulas, while an amazing phenomenon, can allow the passage of fecal matter from the GI tract into the urinary bladder or uterus, where it can create a potentially dangerous infection. Fistulas are common complications of several chronic inflammatory conditions, including Crohn’s disease, ulcerative colitis, and diverticulitis.
Under normal circumstances, we have observed three possible outcomes to the inflammatory response.
Complete resolution. All the damage is confined to highly reproducible cells; no scar tissue develops in the process of repair.
Resolution with permanent tissue damage. This is repaired through the accumulation of scar tissue.
Chronic inflammation. The body is unable to remove the noxious agent, whether it is a pathogen or a toxic substance. An abscess may form to isolate the affected area, or a wider inflammatory response persists and damage accrues, although no significant symptoms may be immediately obvious.
Chronic Inflammation and Diseases
Deeper investigation into the cellular and chemical changes that occur when inflammation is not quickly resolved reveals several intriguing things. We are only recently seeing exactly how, through a combination of oxidative stress (this is cellular damage from the free radicals created by inflammatory chemicals), angiogenesis (the production of new blood vessels to supply nutrition to healing cells—or tumors), infiltration of macrophages into otherwise infection-free tissues, and other issues contribute to the disease process rather than limiting it, which is, after all, what the inflammatory process is supposed to do.
- Inflammation and cancer. The relationship between cancer and inflammation is well established, but is only now becoming well understood. It is most obviously demonstrated with the increased chance (five to seven times higher than the general population2) for people with ulcerative colitis or Crohn’s disease to develop colorectal cancer; with the development of Barrett’s esophagitis, a condition that leads to esophageal cancer—a consequence of untreated gastroesophageal reflux disorder; and with the risk of liver cancer that accompanies long-term, low-grade infections with hepatitis B and C viruses.
It turns out that inflammation supports cancer in several ways: inflammatory chemicals release free radicals that damage cells and may initiate the cellular mutation; inflammatory chemicals stimulate the production of new capillaries that feed cancerous growths; and it has recently been found that many cancer cells metastasize in clumps that contain both lymphocytes and platelets, which allow the cells to attach to new organs and tissues.3
- Inflammation and Alzheimer’s disease. The plaques and tangles that form on neurons in Alzheimer’s disease clearly create an inflammatory response. A new twist now being studied is the result of anti-inflammatory behaviors and a decreased risk of developing this form of dementia. It has been shown that omega-3 oils (the kind available in fish) improve memory and preserve cognition, especially in the earliest stages of Alzheimer’s disease.4 Also, a substance in marijuana proves to have anti-inflammatory (and therefore Alzheimer’s-protective) action in the central nervous system. Work is underway to produce a synthetic form of this chemical that does not have psychogenic side effects.5
- Inflammation and insulin resistance. Insulin resistance is a contributing factor to type 2 diabetes. Obesity-induced insulin resistance is now found to be linked to the presence of macrophages that infiltrate fatty tissue. This presence of these macrophages reliably predicts a significant rise in circulating insulin, while treatment with drugs that improve insulin uptake reliably leads to reduced macrophage activity in fatty tissue.6
- Inflammation and heart disease. That C-reactive protein (CRP) is a player in heart disease isn’t news. However, high CRP levels are now considered as a risk factor for atherosclerosis, heart attack, stroke, and other forms of cardiovascular problems. What is less clear is exactly how this works. CRP, which is manufactured in the liver, is typically considered a chemical associated with acute inflammation,7 but many people evidently make too much of it on a chronic basis. Some studies have now linked heart disease—the classic disease of diet and lifestyle—to chronic, low-grade bacterial or viral infection with Chlamydia pneumoniae, Helicobacter pylori, herpes simplex, or cytomegalovirus.8 All this begs the question, are heart attacks contagious?
- Inflammation and depression. High CRP levels aren’t just associated with cardiovascular disease. Some people who have major depressive disorder also test high for CRP.9 This association is especially common in men. This may also reveal clues into the higher risk of heart attack for people who live with depression.
With all the evidence mounting about chronic inflammation and its association with serious, long-term diseases, we might expect to see a commercial push for the use of more anti-inflammatory medications.
In some cases, such as those people with inflammatory bowel disease, aggressive treatment with anti-inflammatories does have a statistical relationship with lower cancer risks. But for the rest of us, no one is suggesting we all get on long-term doses of NSAIDs (non-steroidal anti-inflammatory drugs) yet. Instead, the healthcare community supports anti-inflammatory behaviors, rather than drugs for the general population. What are those behaviors? Getting omega-3 oils (to reduce CRP), eating a varied diet high in fruits and vegetables (for their antioxidants), exercising, and keeping weight under control (for insulin resistance) are all first-line defenses in the fight against unnecessary and unsuccessful inflammatory action.
None of what you read here today may change the way you massage someone, but maybe it can add to your understanding of the complex nature of health and illness. Our clients often look to us to help them through this complicated maze. While we can’t (and most of us don’t want) to assume the role of doctors, we can be a friendly ear and a well-informed source of good advice. I hope some of this article helps with that.
Ruth Werner is a writer and educator for massage therapists. She teaches several courses at the Myotherapy College of Utah and is approved by the NCTMB as a provider of continuing education. She wrote A Massage Therapist’s Guide to Pathology (Lippincott, Williams & Wilkins, 2005), now in its third edition, which is used in massage schools worldwide. Werner is available at www.ruthwerner.com or firstname.lastname@example.org.
1. Ed Friedlander, “Inflammation and Repair,” www.pathguy.com/lectures/inflamma.htm (accessed fall 2006).
2. Emily Shacter and Sigmund A. Weitzman, “Chronic Inflammation and Cancer,” Oncology 16, no. 2 (February 2002). www.cancernetwork.com/journals/oncology/o0202d.htm (accessed fall 2006).
3. National Cancer Institute Division of Cancer Biology, “Executive Summary of Inflammation and Cancer Think Tank.” http://dcb.nci.nih.gov/thinktank/Executive_Summary_of_Inflammation_and_
Cancer_Think_Tank.cfm (accessed fall 2006).
4. Caroline Cassels, “Omega-3 Supplements Delay Cognitive Decline in Mild Alzheimer’s Disease,” Medscape. www.medscape.com/viewarticle/546415 (accessed fall 2006).
5. MediLexicon International Ltd., “Latest Buzz: Marijuana May Slow Progression Of Alzheimer’s Disease,” 2006. www.medicalnewstoday.com/medicalnews.php?newsid=54534 (accessed fall 2006).
6. Haiyan Xu et al., “Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance,” J. Clin. Invest. 112 (2003): 1821–30. Also available at www.ncbi.nlm.nih.
gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=14679177 (accessed fall 2006).
7. Ed Friedlander, “Inflammation and Repair.”
8. American Heart Association, Inc., “Inflammation, Heart Disease and Stroke: The Role of
C-Reactive Protein,” 2006. www.americanheart.org/presenter.jhtml?identifier=4648 (accessed fall 2006).
9. Marion Danner and others, “Association Between Depression and Elevated C-Reactive Protein,” Psychosomatic Medicine 65 (2003): 347–56. Also available at www.psychosomatic
medicine.org/cgi/content/abstract/65/3/347 (accessed fall 2006).
Schindler, Thomas, et al. 2006. Relationship Between Increasing Body Weight, Insulin Resistance, Inflammation, Adipocytokine Leptin, and Coronary Circulatory Function. JACC 47:1188–95.