05 - Acute and Chronic Inflammation Flashcards
List the clinical signs of acute inflammation
4 (5) functionless tenors: Tumor: Swelling. Rubor: Redness (erythema). Calor: Warmth. Dolor: Pain. Funcio laesa: Function loss.
Compare and contrast the major components of acute and chronic inflammation (including duration, onset, infiltration, fever, WBC count, local features, and vascular changes) (Table 1.5.1)
Acute inflammation –
Duration: Short (days).
Onset: Fast.
Infiltration: Granulocytes (neutrophils).
Fever: Acute onset, fast rising.
WBC count: Increase.
Local features: Cardinal signs (tumor, rubor, calor, palor).
Vascular changes: Vasodilation with increased permeability.
Chronic inflammation –
Duration: Long (weeks-months).
Onset: Insidious (slow).
Infiltration: Agranulocytes (macrophages, lymphocytes, plasma cells).
Fever: Insidious onset, low-grade.
WBC count: Remain constant.
Local features: Slow progressive tissue necrosis, fibrosis.
Vascular changes: New vessel formation (granulation tissue).
Describe the systemic manifestations that indicate presence of inflammation
Fever due to increased blood flow; vasodilation. Increase in peripheral WBC count; emigration of WBCs to site of injury. Increase in plasma protein levels and other “acute phase” reactions.
Define exudate
Inflammatory extravascular fluid containing increased protein, cellular debris (WBC/pus).
Define exudation
Escape of fluid, proteins, and blood cells from the vascular system into the interstitial tissue or body cavities.
Define transudate
Ultrafiltrate of plasma resulting from hydrostatic imbalance across vascular endothelium containing decreased protein.
Define transudation
Transudate being pushed across endothelium because of hydrostatic pressure differences.
Define pus
Purulent inflammatory exudate rich in leukocytes and parenchymal cell debris.
Define edema
Excess fluid in interstitial areas/body cavities from exudate or transudate.
Define effusion
Escape of fluid from anatomical vessels by exudation/rupture.
Sequence of events regarding the changes in vascular flow that occurs in acute inflammation
- Initial transient vasoconstriction (lasting seconds).
- Subsequent vasodilation causing increased blood flow, heat, and redness.
- Increased mean capillary pressure, hydrostatic pressure (capillary bed has an overflow of fluid), and decreased colloid pressure.
- Protein rich fluid (exudates) escape into interstitium (to compensate for the overload of pressure) resulting in net excess of fluid extravasation into interstitial fluid.
- Vascular permeability increases = edema.
Describe the cellular events that result in emigration of leukocytes to the site of injury (Mnemonic): Big picture and step one
Big picture: Deliver leukocytes, ingest offending agents, kill bacteria, degrade necrotic tissues and foreign antigens.
Leukocyte extravasation: Process to deliver leukocytes from blood vessel to area of injury (Marge Rolls Along the Track) –
Margination: Cells move from the center of flowing blood in a vessel to the periphery of the blood flow.
Rolling: Leukocytes roll along the endothelial surface of the vessel.
Adhesion: To endothelial lining via adhesion molecules (selectins, immunoglobulins, integrins).
Transmigration: (aka diapedesis) Cells move through the endothelial cells into tissue.
Describe the cellular events that result in emigration of leukocytes to the site of injury: Steps two and three
Chemotaxis: Process of chemical (chemoattractant) gradients signaling leukocytes toward site of injury. Neutrophils attracted by exogenous substances (bacteria) and endogenous substances (complement, leukotrienes, cytokines); activate leukocytes which release chemical mediators of inflammation.
Phagocytosis (neutrophils and macrophages) –
1. Recognition and attachment: opsonization – coating of microorganism that identifies it as foreign.
2. Engulfment: Surrounds invading microorganism.
3. Killing: Degradation of ingested material.
Describe and discuss the following chemical mediators and their role in inflammation and repair: Vasoactive amines
Vasoactive amines: Preformed and released quickly from mast cells (histamine) and platelets (serotonin).
Histamine: Vasodilation, increases vascular permeability.
Serotonin: Vasodilation, increases vascular permeability.
Describe and discuss the following chemical mediators and their role in inflammation and repair: Kinin system
Bradykinin: Preformed in plasma. Vasodilation, increases vascular permeability, smooth muscle contraction, elicits pain.
Describe and discuss the following chemical mediators and their role in inflammation and repair: Arachidonic acid metabolites
Arachidonic acid metabolites: Located on lipid membrane and formed via cyclooxygenase and lipoxygenase pathways.
Leukotrienes: Increase vascular permeability, mediates chemotaxis.
Prostaglandins: Vasodilation, increases vascular permeability, mediates chemotaxis.
Describe and discuss the following chemical mediators and their role in inflammation and repair: Cytokines
Cytokines: Mediate functions of other cells.
Interleukin-1 (IL-1): Mediates chemotaxis, induces fever, induces WBC release from bone marrow, promotes histamine release.
Tumor necrosis factor (TNF): Induces fever, induces WBC release from bone marrow.
Describe and discuss the following chemical mediators and their role in inflammation and repair: Nitric oxide (NO)
Released from macrophages and endothelial cells. Tissue destruction (cytotoxin) and vasodilation.
Describe and discuss the following chemical mediators and their role in inflammation and repair: Oxygen-derived free radicals
Released from PMNs as peroxide. This unstable molecule upsets the balance of bacterial cell membranes eventually destroying the cell.
Describe acute phase reactions
The subjective description: “I’m sick.” The drastic, sudden feeling that you are sick. Goal following injury to get supplies from blood to tissue. Vasodilation increases blood flow, increase in vascular permeability allows WBC to escape into extravascular space, WBC migrate to site of injury.
List possible outcomes of actue inflammation
Restitution (ideal outcome): Neutralization and/or spontaneous decay of chemical mediators, return of normal vascular permeability, cessation of leukocyte infiltration, death by apoptosis of neutrophils, removal of edema/necrotic debris.
Suppuration/Abscess formation: Collection of walled off area of infection containing purulent material/pus. Occurs with pyogenic organisms (eg staph).
Progression to chronic inflammation: Occurs when acute inflammation cannot be resolved or may have features of chronicity from the outset. Acute/chronic inflammation can coexist.
Repair: Healing by connective tissue replacement (fibrosis) and scarring. Occurs after substantial tissue destruction or when inflammatory response takes place in tissues that do not regenerate.
Describe granulomatous inflammation and identify common causes of granulomas
Special type of chronic inflammation associated with chronic disease states (eg TB, syphilis, sarcoidosis). Granuloma is an aggregation of macrophages that form a particular pattern. May also occur with foreign bodies and insoluble immune particles (eg silicon).
Describe the laboratory diagnosis of acute and chronic inflammation
Acute inflammation –
Examination of exudate: Characteristic high protein levels and specific gravity.
Presence of acute inflammatory cells: Neutrophils (bacterial), lymphocytes (viral).
Biopsy and examination of tissue.
Diagnostic test: Culture, gram-stain, antibody levels, complement levels.
Chronic inflammation –
Biopsy of lesions: Type of chronic inflammation may give clues to etiology.
Microbiologic cultures: Eg, wound cultures.
Immunologic studies: Eg, syphilis.
Serologic studies: Eg, antibodies against syphilis, fungi, etc.
Skin test: Eg, TB, fungus.
Serum autoantibody levels: Eg, autoimmune disease.
Describe theapproach to treating inflammation
Cyclooxygenases and lipooxygenases (bad guys): Enzymes that synthesize arachidonic acid metabolites which are powerful mediators of endothelial injury and tissue damage.
NSAIDs: Inhibit cyclooxygenase (COX) preventing prostaglandin production, which are prostaglandins and thromboxanes (involved in pathogenesis of pain and fever).
Steroids: Similarly prevent the formation of arachidonic acid except they inhibit phospholipases.
COX-2 inhibitors: Block COX-2 in the cyclooxygenase pathway.
Describe primary intention wound healing
Take two edges and put them together. Heals with very little scarring.
Describe secondary intention wound healing
Healing by outside in (leaves it open and oxygenated).
Describe tertiary intention wound healing
Leave it open for several days and then close up (eg dog bite). Intentionally delayed primary closure.
Describe abrasion
A scrape, like road rash, usually just damage to the epidermis.
Describe laceration
Cut into the skin, usually accidental (eg pt with a cut).
Describe incision
Intentional cut into skin, reserved for medical procedures (eg surgical opening).
Describe crush
Trauma incident. Clinical considerations include skin, underlying tissue, nerve and bone destruction.
Describe degloving
Complete removal of skin from a circular area (eg digit, scalp, limb).
Describe puncture
Entrance of a foreign object into the tissue (eg needle stick) These are likely to become infected because any bacteria in the wound now have an anaerobic environment to grow.
Describe avulsion
Tearing away of skin and underlying tissue from its points of attachment.
Describe bite
Usually from an animal. Clinical considerations include skin and underlying tissue destruction and bacterial infection.
Discuss the phases of wound healing
Inflammation: Body’s response to injury (typically locally) by containing and isolating the area, destruction of microorganisms, inactivation of toxins.
Epithelialization: Thin layer of cells develops over a cut or laceration and helps keep out bacteria. This occurs within 24-48 hours for small wounds/incisions.
Collagen synthesis: Over the course of 4-6 weeks, collagen, a connective tissue, is produced by myofibroblasts in the wound area and over time mature and become strong. Often returning the previously injured area to its former strength.
Scar maturation: Strength of the new fibrotic tissue is not achieved until maturation of the scar is complete, often taking up to a year. Prior to maturation, strains on the scar should be avoided to prevent breakdown of the delicate and immature collagen fibers.
Organization: (Not a step in and of itself) The process by which exudate remaining in the tissue, along with myofibrils and ingrowing capillary beds gather, grow and align so proper healing and scar formation can occur.
