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Inflammation

 

Outline

The inflammatory response (both acute and chronic)

(a set sequence of physiological behaviors that occurs in response to injury by a non specific agent)

Acute Inflammatory Response

1.Purpose

1.to neutralize or destroy foreign material

2. restrict tissue damage

3. alert individual to impending threat of tissue injury

4. prepare injured area for healing

2.Causes

1.trauma

2.surgery

3.infection

4. caustic chemicals

5. extremes of heat or cold

6. immune responses

7. ischemic damage to body tissue

3. Cardinal Signs of Inflammation

1. rubor (redness)

2. tumor (swelling)

3. calor (heat)

4. dolor (pain)

4.Hemodynamic (Vascular Changes)

momentary constriction followed by vasodilation of arterioles and venules

increase in capillary permeability

5. Cellular changes

role of white blood cells

mast cells

neutrophils

eosinophils

macrophages

margination (pavementing)

diapedesis

chemotaxis

phagocytosis

6.Chemical Mediators Involved

Histamine

Plasma proteases

kinins

complement

clotting factors

prostaglandins

PGE1 and PGE2

Prostaglandin thromboxane A2

Prostacycline -PG12

leukotrienes

SRSA (slow reacting substance of anaphylaxis

platelet activating factor (PAF)

cytokines

7. Inflammatory exudates

Serous

Fibrinous

Membranous

Purulent (suppurative)

abscess

cellulitis

Hemmorhagic

8. Resolution of Acute inflammation

leukocytosis

fever

metabolism

ESR (erythrocyte sedimentation rate)

plasma iron levels

skeletal muscle catobolism

anorexia

lassitude and sleep

production of acute phase proteins by liver

Chronic Inflammation

compared to acute inflammation it is characterized more by infiltration of mononuclear cells, rather then neutrophils and by proliferation of fibroblasts rather then formation of exudates

it is often provoked by low grade irritants

it can invole one of two patterns

nonspecific – diffuse accumulation of macrophages and lymphocytes

granulomatous – involving formation of a granuloma

1.Capillary membrane enlarged to show endothelial cells and basement membrane

2.Blood flow through capillary showing neutrophils, eosoinophils, monocytes and platelets. Mast cell in tissue with antigen nearby

3.Margination

4. Diapedesis

5. Phagocytosis

Discussion

Capillary permeability is a very important concept. As permeability increases, the space between the endothelial cells increases, allowing more fluid, proteins, cells and other materials to leak out or move out into the surrounding tissue. Many substances involved in the inflammatory response increase capillary permeability, for example, histamine, SRSA and so on.  This allows for wbc and other substances to penetrate the tissue where antigen is often located, but it can have consequences. It can lead to swelling and the loss of fluid from the intravascular space.

    Inflammation is usually a localized event . Hence, the four cardinal manifestations of inflammation reperesent clinically observable symptoms in the local area   (swelling, redness, pain and heat) . Swelling is due to the accumulation of fluid in the tissue, redness is due to increased blood flow to the area, pain is due to the action of bradykinin and prostaglandins on local nerve tissue and heat is due to increased blood flow to the area. However, inflammation can often have systemic effects. For example, fever. Fever is triggered when the hypothalamus's set point is changed by the action of cytokines. These cytokines come from wbc in response to pyrogens released by microrgnaisms, or sometimes, simply as a response of wbc to other injured cells (as occurs in cases or myocardial infarction, pulmonanry emboli and neoplasms). The cytokines reponsible are interleukin- 1, interleukin 6 and tumor necrosis factor. Fever itself is an adaptive reponse. It increases wbc motility, stimulates interferon production and activates T cells. It also inhibits the growth of many microrganisms. 

Clinically Speaking

  Asthma is a good illustration of the adverse effects of inflammation. Basically, a person with asthma has an inappropriate inflammatory response in lung tissue. What triggers off this response can vary from person to person. In some it may be exposure to an allergen such as dust. In others it can be changes in air temperature (especially cold air), exercise, second hand cigarrete smoke, or any of a variety of other stimuli. In reponse to the stimulus, histamine and SRSA is released by mast cells and bring about three important  physiological changes in the bronchioles: a) they  alter capillary permeability of the blood vessels surrounding the bronchiole, this allows fluid to leak into bronchial tissue causing edema of the bronchiole , b) they constrict the smooth muscle surrounding the bronchiole and c) they increae the release of mucus into the airway. All three of these events cause a narrowing of the airway, making it more difficult to breathe.
    By understanding the pathophyiology of the asthmatic inflammatory response, we can also understand why certain drugs are effective in the treatment of asthma.
• Beta agonists- these are drugs that stimulate the sympathetic nerve system by mimicking the action of epinephrine. The bronchioles are innervated by Beta2 receptors which when activated by the SNS cause bronchodilation
• Steroids- Steroid drugs suprress the inflammatory response, as well as other aspects of the immune reponse
• Cromolyn- this drug can be used to prevent asthmatic attacks- it works by stabilizing the membrane of the mast cell and, therefore, decreasing its ability to release histamine
• Leukotriene inhibitors- this is a new class of drugs being used to treat asthma. these drugs, as the name implies, inhibit the synthesis of leukotrienes by the mast cell

The liver and white blood cells produce what are known as acute phase reactants, substances which are often involved in the inflammatory reaction. These substances would be elevated in cases of inflammation. Four of these are as follows:

Substance

Normal Range (Adults)

Comment
C3 83-177mg/dl Central component of the complement system
C-reactive protein 6.6-820ug/dl Smilar to IgG but not antigen specific. Activates complement
ESR (erythrocyte sedimentation rate) 0- 20 mm/h It is a measure of rbc activity that is efeected by the levels of fibrinogen
fibrinogen 200-400mg/dl Important component of clotting , often rises seven fold during inflammation

 

Text
McCance K. & S. Heuther. (1998). Pathophysiology: The Biologic Basis for Disease in Adults and Children. C.V. Mosby  (NY). Chap 7