All organisms respond to local injury.
The inflammatory process is the reaction of blood vessel, which brings about an accumulation of fluid and white blood cell in the extravascular tissue.
Inflammation and repair go hand in hand.
Inflammation is a protective response:
*Rid organism of cause of injury (microbe, toxin)
*Rid the organism of consequences of injury (necrotic cells)
*Without wounds would never heal
Inflammation and repair can be harmful thus leading to:
* Unnecessary scarring
Inflammatory response occurs in vascularized connective tissue.
Intravascular Cells important to inflammation are:
- “Polymorphonuclearleukocyte” nickname “poly” looks like it has lots of nuclei but really only has one. Polys, like basophils and eosinophils, are called “granulocytes“. That is because there is lots of little granules coving the surface of the cells. The granules are really lysosymes with protolytic enzymes that destroy foreign substances. Neutrophils are called neutrophils because when you stain them they pick up the red and blue dye equally. Most common in circulation. Make up 50-70% of the differential. When they leave circulation they are mobile and can become phagocytic. The hallmark of acute inflammation. They are the first WBC to get to the site of inflammation.
Stab cells are immature polys (neutrophils). When a really bad infection is present, bone marrow releases immature polys (stabs cells or bands)– shift to the left.
Polys,segs,and neutrophils are all same, represent mature cells.
- Granulocytes that stain red. The make up 1-2% of differential. See increased numbers in response to parasite infection and allergies. When you inject cortisone, number of eosinohpils decreases. Circadian rythm – amount of cortisone released from adrenal gland varies over 24 hours and number of eosinophils vary inversely with the amount of cortisone you produce. Alot of research being done with eosinophils and asthma.
- Granulocytes that stain blue. They make up 1% or less of differential. Least common of WBC. Mast cells and basophils are basically same but mast cells are found outside blood vessel. The store house for histamine. Mast cells are very important in hypersensitivity reactions (allergy).
- No granules. Large round cells. Found in the lymph nodes and follicles. Start out in bone marrow and migrate to lymph. Two major kinds: T-Cells and B-Cells. Make up 25-33% of differential count. Have random mobility (not as much but some). Appear late in inflammatory response. Plasma cell is a type (B-cell) of lymphocyte. Generally represent chronic inflammation. Mildly phagocytic and also under control of steroids.
- Called a macrophage or histiocyte when it is outside blood vessel or in tissue. Make up 4-6% of WBC. Extremely phagocytic. Extremely mobile. Can also release powerful chemicals. Important in the immune response because they introduce the antigen to they lymphocytes. The second line of defense at the site of injury. Neutrophils get there first, as they die, the environment gets more acidic, the macrophage can withstand acidic environment, they then phagocytize debris. Macrophages can form giant cells, langhan cell (when they fuse together). These cells are found in TB and other chronic infections.
Systemic changes in WBCs:
*A healthy individual has 6-10,000 WBC/cmm of blood. With inflammation it’s called leukocytosis, and have more than 30,000 WBC/cmm blood.
*Most of increase is due to neutrophils.
*Leukopenia – a decrease in number WBCs. Seen in typhoid, TB, cancer tx.
Cells outside the vessels which are important are:
— Mast cells (basophil)
Inflammation is divided into acute and chronic
*Acute is of short duration, primary cell is the neutrophil, characterized by exudation of fluid and plasma proteins.
* Chronic is longer, main cells are lymphocytes and macrophages, proliferation of blood vessels, fibrosis and necrosis. This means you see alot of scar tissue with chronic inflammation. Hallmark is scar tissue.
Vascular and cellular responses of both acute and chronic are mediated by chemical factors derived from cells and plasma and triggered by the inflammatory stimulus. Necrotic cells, themselves, release these chemical. These are called chemical mediators of inflammation. Inflammation stops when the injurious stimulus is removed.
Acute inflammation has three major components:
* Alteration in vessels leading to increased blood flow to the area.
*Structural changes in microvessels that allow plasma protein and WBCs to leave the circulation. Capillaries are composed; endothelial cells and fluid leaves the capillary at the junction between the endothelial cells. Inflammatory stimulus causes these junctions to open up widder than normally which allows excess fluid to get out of vessel. After fluid leaves vessel the blood get thicker because of large protein particles and cells which stay inside vessel. This is referred to as stasis because the blood flow slows down. Now the white blood cells start to line up along the peripheral edges of the vessel. This is called margination or pavementing.
*Emigration of WBCs from vessels so they can accumulate at the site of injury.
Vasodilatation occurs resulting in increased blood flow to the area. New capillary beds open up. (HEAT AND REDNESS). This is followed by slowing of the circulation that is brought about by increased permeability. Fluid moves into the extravascular space, the blood becomes thicker and thus moves more slowly. At this point the blood is more viscous; there are a higher concentration of RBCs in the vessels. We call this stasis.
When stasis occurs the WBCs start to move toward the periphery of the vessel. This is call
margination or pavementing.
The hallmark of acute inflammation is increased vascular permeability leading to edema.
How does excess fluid get out of the vessels?
* Endothelial gaps. Gaps are do to endothelial contraction mediated by histamine, bradykinin, leukotrienes, substance P and others.
* Direct endothelial injury by burns, lytic bacterial infections.
*Delayed prolonged leakage beginning after a delay of 2 to 12 hours. Usually caused by thermal injury, radiation and certain bacterial toxins. An example is a late occurring sunburn.
*Leukocyte-mediated endothelial injury. Seem mostly in the kidneys and lungs and is related to a hypersensitivity reaction.
*Leakage from new blood vessels which have lots of receptors for chemical mediators.
*Margination, cells have to adhere to vessels. There are adhesion receptors and chemical mediators that allow this to happen. There are genetic disorders where people can not make adequate adhesion factors; these people can not mount a normal inflammatory response.
*Transmigration – leaves the blood vessel.
*Migration, leukocytes emigrate to the site of injury by a process called chemotaxis. Chemotactic factors can be both endogenous and exogenous. Bacterial products are the most common exogenous factors. Endogenous agents include components of compliment, leukotrienes and cytokines. Chemotactic factors stimulate locomotion.
Phagocytosis is the ability of the WBC to recognize the pathogen, form an attachment, engulf it and kill it. Various chemical mediators are important in this function. Bacterial killing is accomplished mostly by an oxygen-dependent mechanism. Killing can also occur by the release of granules from the lysosomes.
Examples of inflammatory lesions:
Examples: abcess local collection of pus walled off from rest of body; will always get some scarring. The body reabsorbs the pus or us can drain the abcess. Sinus or fistula can form from an abcess.
Cellulitis is a spreading diffuse edematous, purulent, inflammation and it is usually due to bacteria that contains an enzyme that breaks down fibrin.
Ulcer is excavation produced by the shedding of inflammatory necrotic tissue into a cavity. Three major areas where you see ulcers, GI tract, Cervix of uterus, lower extremities: legs.
Age, nutritional status, health, circulatory system, impact on whether a person can mount an inflammatory/immune response.