Patho chapter 3

cellular response depends on

ability of cells, primarily leukocytes, erythrocytes, platelets to migrate/move across endothelial cells + get to exact site of injury

process of inflammation requires

ability to recognize injury, activate response, appropriately shut down response when injury has passed result: either tissue repair or regeneration or formation of scar tissue

blood vessels dilate (widen) to

accommodate increased blood flow to site of injury

inflammatory mediators can circulate continuously w/in blood plasma

accomplished thru work of 3 major interrelated pathways pathways responsible for activation + deactivation of inflammatory mediators that circulate in plasma

mucous membranes purpose

areas not covered by skin protected by this chemical barrier helps to neutralize or destroy many harmful invaders

Cellular adherence

attraction + binding is another step essential for effective phagocytosis

loss of ability to shut down inflammatory response effectively can lead to

autoimmunity- self attack against body tissues

Tears and saliva

ex. enzyme filled fluids that bathe mucous membranes + offer essential protection to eyes + oral cavity

Kinin pathway

Source of highly potent vasoactive inflammatory mediators amplifies inflammatory response by triggering other inflammatory mediators

Why are multiple sources + pathways needed to induce + suppress inflammation?

inflammatory response must occur to heal tissues + inflammatory mediators are so potent + powerful that multiple pathways needed to regulate these substances

non pharmacologic treatments for inflammation include

initial- rest, ice, compression, elevation resolution may improve w/ application of of warmth/heat + increased movement

ex of cytokines

interleukins, growth factors, interferons, chemokines

injury ex.

invasion by microorganisms, cellular mutations, hypoxia or anorexia, nutritional deficiencies, physical or chemical damage

cardinal signs

local manifestations of acute inflammation includes erythema (redness), heat, swelling, pain, loss of function

cytokines released from lymphocytes called

lymphokines

initial steps in inflammatory response influenced by vasoactive inflammatory mediators:

tissue injury blood vessel vasodilation increased vascular permeability activation of clotting cascade continued release + circulation of vasoactive inflammatory mediators

acute inflammation triggered by

tissue injury + essential for healing

lining of blood vessel becomes more permeable (loosens)

to allow cells to easily move from vessel into injured tissue must occur w/ basement membrane of blood vessel + adjacent endothelial cells

molecule receptors

to attract cells needed to form structural matrix

proteinases (enzymes)

to degrade dead tissue

proteinase inhibitors

to prevent healthy tissue breakdown

inflammatory mediators

to promote chemotaxis to affected area

growth factors

to promote regeneration of new cells + tissues

adhesion molecules

to provide "stickiness" to these cells

matrix or structural proteins

to rebuild architectural supports

clotting (coagulation) factors

to stop bleeding + form fibrin clot

impaired inhibition of inflammation can lead to

uncontrolled inflammatory response, depletion of proteins needed w/in 3 pathways

main point: potent inflammatory mediators are released from

variety of white blood cells in order to effectively orchestrate inflammatory process

local manifestations primarily related to

vasodilation + fluid accumulation in tissues as result of activation of inflammatory mediators

serotonin causes

vasodilation + increased vascular permeability, allowing cells of healing to arrive quickly to site of injury

exudate

watery fluid accumulates at site of injury has high protein + leukocyte concentration sign: vessels have become more permeable, cells active in phagocytosis are present + ready to fend off microorgan. healing can then begin

basophil

white blood cell that also contains granules

protection of body depends on 3 lines of defense

1. 1st line of defense- relies on protection of skin + mucous membranes 2. 2nd line of defense- effective inflammatory response 3. 3rd line of defense- activated thru specificity of immune response

3 steps needed for successful cellular response:

1. Chemotaxis 2. Cellular adherence 3. Cellular migration

increased blood + fluid needed at site of injury for 2 reasons:

1. blood is composed of cells active in phagocytosis (engulfing + removing harmful agents), cells essential in promoting healing + developing immune response 2. increased fluid dilutes harmful substances at site of injury

3 goals of acute inflammatory response

1. increase blood flow to site of injury (vascular response) 2. alert products of healing to attend to site of injury (cellular response) 3. remove injured tissue + prepare site for healing

cellular adherence regulated by:

1. inflammatory mediators (chemotactic factors released by endothelial cells) 2. Receptors that bind leukocytes to surface of endothelial near site of injury

initial treatment principles for acute inflammation:

1. reduce blood flow to local area 2. decrease swelling 3. block action of various inflammatory mediators 4. decrease pain

2nd line defense (inflammatory response) activated when

1st line of defense is inadequate nonspecific- process of waging inflammatory response is identical regardless of cause of injury

plasma proteins increased as result of

3 plasma protein systems proteins called acute phase reactants + can be measured thru use of lab tests (C reactive protein)

cellular migration

3rd essential step in cellular response

typically individual has white blood cell count of

5,000 to 10,000/mm3

placement of mast cell

allows for rapid response directly at site of injury

chronic inflammatory response

altered inflammatory response due to unrelenting injury

injury

broad sense to include any form of damage or alteration to cells or tissues

inflammatory mediators w/in cells generated in

cell plasma membrane or made up of proteins w/in cell

diapedesis

cells can move between + thru endothelial junctions

after vessels are dilated + permeable

cells essential for healing are needed at injury site

white blood cells

commonly produce + release inflammatory mediators platelets, endothelial cells, injured tissue cells are potential sources

3 pathways if inflammatory mediators in plasma

complement, clotting, kinin

vessel walls function

confine blood cells + plasma w/ injury- must be loosened to allow for movement of healing fluids + cells into damaged tissues

inflammatory mediators released from platelets + other cells

constrict blood vessels + form clot at the site

hypothalamus responsible for

controlling body temperature

goal of tissue healing + repair

cover wound, clear debris, restore structural + functional integrity of injured area 3 phases: inflammatory, proliferative, remodeling structural supports must be rebuilt + functional cells + tissues regenerated or replaced

what is a common occurrence in acute inflammatory response?

damage to healthy surrounding tissue

protective scab formed from

dried blood + exudate

leukocytosis

elevation in white blood cells or leukocytes w/ count usually above 10,000/mm3 increased circulation of white blood cells to aid in healing

lymphadenitis

enlargement + inflammation of nearby lymph nodes can occur as function of filtering or draining harmful substances at injury site

acute inflammatory response

expected body response to injury

inflammatory mediators (vasoactive)

facilitate process of widening + loosening of blood vessels at site of injury located in blood plasma + many cells (platelets, mast cells, basophils, neutrophils, endothelial cells, monocytes, macrophages)

pyrexia

fever, elevated core body temp result of inflammatory mediators acting directly on hypothalamus

systemic manifestations related to inflammatory response include

fever, leukocytosis, higher percentage of circulating plasma proteins

leukocyte is global term

for many different types of white blood cells neutrophils, monocytes, macrophages, mast cells, basophils, T + B lymphocytes

endothelial cells

form tight junction w/in inner lining of blood vessels + lymphatic vessels of heart connected to basement membrane

signals to trigger, enhance, + discontinue inflammatory response

generated w/in other white blood cells (lymphocytes, monocytes/macrophages)

corticosteroids

highly effective group of anti inflammatory drugs that work to block production of arachidonic acid + then decreasing inflammatory response have role in inhibiting immune response

ex of inflammatory mediators released by mast cells

histamine, leukotrienes, prostaglandins

cellular response is also regulated by

inflammatory mediators like the vascular response

mast cells

important inflammatory mediator leukocytes (white blood cells) that are housed thuout CT of body + near all blood vessels

impaired activation of inflammation can lead to

inadequate blood flow to injured area impair healing by limiting phagocytosis, clot formation, + repair of injured tissues

what happens during phagocytosis?

inflammatory cells release inflammatory mediators to attract more neutrophils

degranulation

mast cell breaks apart + releases inflammatory mediators in form of extracellular granules (grain like particles)

breaks in skin + mucous membranes or loss of protective fluids causes:

microorganisms + other harmful agents to enter body + threaten homeostasis

goal of treatment

minimize damage to healthy, unaffected tissue + promote rapid healing

tissue destruction

minimized by work of inhibitor proteins in plasma derived complement, clotting, kinin systems

cytokines released from monocytes or macrophages called

monokines

cytokines

more than one hundred distinct cell proteins most often found w/in white blood cells that have vital role in regulating inflammation

pharmacologic (drug) treatments for inflammation

most commonly block action of inflammatory mediators this reduces swelling, pain, redness, warmth - typical of inflammation

cytokines active from

onset of vasodilation + increased vascular permeability to resolution of inflammatory response

basement membrane

outer membrane of vessels separates vessel from tissues of body

inflammatory response has multiple components + often considered

overzealous- explains efforts of booming pharmaceutical industry to find effective anti inflammatory drugs

elevated body temp stimulates

phagocytosis + can also inhibit growth of certain microorganisms

skin and mucous membrane function

physical + chemical barrier to invasion 1st line of defense

inflammatory mediators released from endothelial cells or injured tissue cells ex.

platelet activating factor- complex lipid stored in cell membranes (endothelial cells) that line blood vessels + in many other types of cells that can become injured arachidonic acid

platelet activating factor

potent inflammatory mediator key role in promoting vessel vasodilation, clotting, attracting infection-fighting white blood cells to site of injury

neutrophil releases

potent inflammatory mediators as it works to engulf + digest impaired tissue unaffected healthy tissue also destroyed

Chemotaxis

process of moving certain cells to site of injury

mast cell is responsible for

production + immediate release of inflammatory mediators thru degranulation

platelets active in generating + releasing inflammatory mediators to

promote vasodilation, clotting, attraction of white blood cells, healing in injured tissues

Clotting pathway

promotes coagulation thru cascade of clotting factors suppresses coagulation when clotting is complete various clotting factors produce + release inflammatory mediators

inflammatory mediators associated w/ arachidonic acid

prostaglandins, lipoxins, leukotrienes, thromboxane- active in processes of vasodilation + vasoconstriction, increasing vascular permeability, bronchodilation + bronchoconstriction, attraction of leukocytes

thrombus

protective clot + subsequent scab

tissue injury requires

response at level of blood vessel near site of injury clotting + healing must occur to prevent infection

acute inflammatory response is

self limited offending agent has been destroyed + removed- feedback systems regulated by 3 plasma protein systems along w/ relevant inflammatory mediators, deactivate inflammatory response, allowing tissue to heal

example of inflammatory mediator found in platelets

serotonin, histamine

Complement pathway

several proteins that comprise 10-15% of plasma; produced in liver triggered by presence of microorganisms once triggered- activates cascade of inflammatory mediators primary role to destroy + remove microorgan. to prevent infection thru (opsonization- making bacteria vulnerable to phagocytosis), cell lysis (destruction)

skin's purpose

skin allows protective physical barrier against harmful substances in external environment

immune response wages...

specific disease depending on type of invader

chemotactic factors

specific inflammatory mediators that are activated which attract specific types of cells (neutrophil chemotactic factor attracts neutrophils)

arachidonic acid

substance derived from plasma membrane of injured cell which generates various inflammatory mediators thru complex chemical conversion