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What happens during acute inflammation?
Within a few seconds or minutes after tissue is injured, acute inflammation starts to occur. The damage may be a physical one, or might be caused by an immune response.
Three main processes occur before and during acute inflammation:
- Arterioles, small branches of arteries that lead to capillaries that supply blood to the damaged region dilate, resulting in increased blood flow
- The capillaries become more permeable, so fluid and blood proteins can move into interstitial spaces (spaces between cells)
- Neutrophils, and possibly some macrophages migrate out of the capillaries and venules (small veins that go from a capillary to a vein) and move into interstitial spaces. A neutrophil is a type of granulocyte (white blood cell), it is filled with tiny sacs which contain enzymes that digest microorganisms. Macrophages are also a type of white blood cells that ingests foreign material.
Klaus Ley, M.D., a scientist at the La Jolla Institute for Allergy & Immunology, reported in a study published in Nature that neutrophils are the human body's first line of defense; they are the main cells that protect us from bacterial infections. Their protective function is a positive one, however, they also have inflammatory properties that may eventually lead to heart disease and several autoimmune diseases, such as lupus. Effectively manipulating neutrophils is vital in disrupting inflammatory diseases.
When our skin is scratched (and the skin is not broken), one may see a pale red line. Soon the area around that scratch goes red, this is because the arterioles have dilated and the capillaries have filled up with blood and become more permeable, allowing fluid and blood proteins to move into the space between tissues.
Edema - the area then swells as further fluid builds up in the interstitial spaces.
An ingrown toenail with the five PRISH signs.
The five cardinal signs of acute inflammation - "PRISH"
- Pain - the inflamed area is likely to be painful, especially when touched. Chemicals that stimulate nerve endings are released, making the area much more sensitive.
- Redness - this is because the capillaries are filled up with more blood than usual
- Immobility - there may be some loss of function
- Swelling - caused by an accumulation of fluid
- Heat - as with the reason for the redness, more blood in the affected area makes it feel hot to the touch.
The five classical signs of inflammation
Although Latin terms are still used widely in Western medicine, local language terms, such as English, are taking over. PRISH is a more modern acronym which refers to the signs of inflammation. The traditional Latin based terms have been around for two thousand years:
- Dolor - Latin term for "pain"
- Calor - Latin term for "heat"
- Rubor - which in Latin means "redness"
- Tumor - a Latin term for "swelling"
- Functio laesa - which in Latin means "injured function", which can also mean loss of function.
Dolor, Calor, Rubor, and Tumor were first described and documented by Aulus Cornelius Celsus (ca 25 BC-ca 50), a Roman encyclopaedist. Celcius is famous for creating De Medicina, which is thought to be the only surviving section of a vast encyclopedia. De Medicina was the main source of medical reference in the Roman world for pharmacy, surgery, diet and some other medical fields.
Functio laesa - it is not clear who first described and documented the fifth sign. The majority of attributions have gone to Thomas Sydenham (1624-1689) an English physician and Rudolph Carl Virchow (1821-1902), a German doctor, biologist, politician and pathologist. Virchow is seen as one of the founders of social medicine.
These five acute inflammation signs are only relevant when the affected area is on or very close to the skin. When inflammation occurs deep inside the body, such as an internal organ, only some of the signs may be detectable. Some internal organs may not have sensory nerve endings nearby, so there be no pain present, as is the case with some types of pneumonia (acute inflammation of the lung). If the inflammation from pneumonia pushes against the parietal pleura (inner lining of the surface of the chest wall), then there is pain.
Acute and chronic inflammation compared
The lists below show the difference between chronic and acute inflammation regarding the causative agents, which major cells are involved, features regarding onset, duration, and outcomes:
- Causative agents - harmful bacteria or injury to tissue
- Major cells involved - mainly neutrophils, basophils (in the inflammatory response), and eosinophils (response to parasites and worms), and mononuclear cells (macrophages, monocytes)
- Primary mediators - eicosanoids, vasoactive amines
- Onset (when does the inflammation start) - straight away
- Duration - short-lived, only a few days
- Outcomes - the inflammation either gets better (resolution), develops into an abscess, or becomes a chronic inflammation.
- Causative agent - non-degradable pathogens that cause persistent inflammation, infection with some types of viruses, persistent foreign bodies, overactive immune system reactions
- Major cells involved - Macrophages, lymphocytes, plasma cells (these three are mononuclear cells), and fibroblasts
- Primary mediators - reactive oxygen species, hydrolytic enzymes, IFN-γ and other cytokines, growth factors
- Duration - from several months to years
- Outcomes - the destruction of tissue, thickening and scarring of connective tissue (fibrosis), death of cells or tissues (necrosis).
Sleep quality and duration impacts on inflammation risk
Scientists at Emory University School of Medicine in Atlanta, Georgia, found in a study that sleep deprivation or poor sleep quality raises inflammation, which in turn increases the risk of developing heart disease and stroke.
The team gathered data on 525 middle-aged volunteers who had completed the Pittsburgh Sleep Quality Index (PSQI) questionnaire, which asked detailed questions about sleep quality and duration.
They tested the participants' levels of various inflammatory markers, and then tried to see whether they could link them to quality and duration of sleep.
The authors concluded:
"Poor sleep quality, and short sleep durations are associated with higher levels of inflammation."
Why does inflammation cause pain?
When people have inflammation it often hurts, they feel pain, stiffness, discomfort, distress and perhaps agony, depending on the severity of it. Pain can be constant and steady, in which case it is often referred to as an ache. Pain can be of a throbbing type, a pulsating pain, or it can be a stabbing or pinching pain.
Pain is a very individual experience and the only person who can describe it properly is the one who is feeling it.
Pain can be acute or chronic. It can also be:
Specific receptors are stimulated for us to feel this type of pain. These receptors sense changes in temperature, vibration, stretch, and chemicals which damaged cells release. "Nociceptive" means causing or reacting to pain - the cause of the pain comes from outside the nervous system, and the nervous system reacts to it. "Non-nociceptive" means the pain comes from within the nervous system itself.
This is a kind of nociceptive pain. The sensation is felt in muscles, joints, bones, ligaments, and on the skin. Musculo-skeletal pain is somatic pain. Pain receptors are sensitive to: stretch in the muscles, vibration, temperature, as well as inflammation. When there is a lack of oxygen there may be painful ischemic muscle cramps.
Somatic pain tends to be sharp and localized - touching or moving the affected area will result in more severe pain.
This is a kind of nociceptive pain. Pain is sensed deep down in the body, in the internal organs and main body cavities, such as the heart, lungs, bowels, spleen, liver, kidneys, bladder, uterus, and ovaries. The nociceptors (pain receptors) sense oxygen starvation (ischemia), stretch, and inflammation. It is harder to localize visceral pain than somatic pain. The pain is usually described as a deep ache. Cramping and colicky sensations are examples of visceral pain.
Inflammation primarily causes pain because the swelling pushes against the sensitive nerve endings, which send pain signals to the brain. Nerve endings send pain signals to the brain all day long; however, it learns to ignore most of them, unless pressure against the nerve endings increases.
Other biochemical processes also occur during inflammation which affect how nerves behave, and cause pain.
Inflammation risk much greater if you are obese
Fat men have more inflammatory markers (white blood cells) than men of the same age who are not obese or overweight.
example of common painful joints in an overweight male
Raised white blood cell levels are markers which are linked to a higher risk of developing various illnesses, including coronary heart disease.
In a recent study, a team from Pennington Biomedical Research Center in Baton Rouge, Louisiana, focused on specific types of white blood cells; neutrophils, lymphocytes, monocytes, basophils, and eosinophils.
They measured resting levels of the white blood cells in the adult males, as well as their levels of fitness and BMIs (body mass indexes), and adjusted the results for age.
They found that:
- Unfit men had higher white blood cell levels than fit men
- Men with higher BMIs had raised levels of white blood cells
- The combination of fitness levels and body weights impacted considerably on levels of white blood cells, and ultimately inflammation.
Although scientists know that inflammation plays a key role in heart disease and several other illnesses, what drives inflammation in the first place is still a mystery.
Inflammation drops when women lose weight - scientists at the Fred Hutchinson Cancer Research Center in Seattle, Washington found that postmenopausal overweight or obese women who lost 5% or more of their body weight had measurable falls in levels of inflammation markers. Team leader, Anne McTiernan, M.D., Ph.D., said "Both obesity and inflammation have been shown to be related to several types of cancer, and this study shows that if you reduce weight, you can reduce inflammation as well."
Autoimmune disorders and inflammation
An autoimmune disease, also known as autoimmune disorder, is one where the body initiates an immune response to healthy tissues, mistaking them for harmful pathogens or irritants. The immune response triggers an inflammatory response too.
There are literally hundreds of autoimmune diseases, and nearly all of them have inflammation as one of the signs, examples include:
- Rheumatoid arthritis - there is inflammation in the joints, tissues surrounding the joints, and sometimes some other organs in the body
- Ankylosing spondylitis - there is inflammation of the vertebrae, muscles, ligaments, and also the sacroiliac joints (where the spine and hips meet)
- Celiac disease - there is inflammation and destruction of the inner lining of the small intestine
- Crohn's disease - the gastrointestinal tract becomes inflamed. Inflammation is most common in the ileum (small intestine), but may occur anywhere in the GI tract, from the mouth to the anus
- Fibromyalgia - often a set of symptoms related to another autoimmune disorder, such as lupus or rheumatoid arthritis. There is pain in various parts of the body. Location and even the existence of inflammation is unclear
- Graves' disease - one of the signs is goiter; when the thyroid gland is inflamed. Exophthalmos, inflammation of the muscles behind the eyes. Grave's dermopathy, inflammation of the skin, usually the shins and the top of feet (uncommon)
- Idiopathic pulmonary fibrosis - the role of inflammation is unclear. Experts used to think that the disease was mainly caused by inflammation within the alveoli (tiny sacs within the lungs). However, treatments to reduce inflammation are often disappointing. Therefore, although there is inflammation, its impact on the disease is a mystery
- Lupus - there can be inflammation in the joints, lungs, heart, kidney and skin
- Psoriasis - there is inflammation of the skin. In some cases, as in psoriatic arthritis, the joints and tissue surrounding the joints may also become inflamed
- Type 1 Diabetes - inflammation in various parts of the body are likely if the diabetes is not well controlled
- Addison's disease - inflammation of the adrenal glands. The stress to the body caused by this disease can also lead to inflammation elsewhere
- Vaslculitis - refers to a group of disorders in which inflammation eventually destroys blood vessels, both arteries and veins
- Transplant rejection - there is already substantial inflammation caused by the transplant operation. If the organ recipient's immune system rejects the new organ, there is typically inflammation in and around the donated organ
- Various allergies - all allergies have inflammation. Asthma has inflammation of the airways, in hay fever the nose, ear and throat mucous membranes become inflamed, people who are allergic to bee stings may have serious life-threatening inflammation which affects the whole body (anaphylaxis)
- Vitamin A deficiency - inflammatory responses are much more likely if the person is deficient in vitamin A.
The disorders mentioned above are just a tiny example of the hundreds of autoimmune disorders which have inflammation as one of their signs.
On the final page we look at treatments for inflammation, including medicines, herbs with anti-inflammatory properties and other methods of treatment.