NURS 250 ch 5 Innate Immunity: Inflammation and Wound Healing

You suspect that a patient is having an acute inflammatory response. List three tests that can be used to confirm this suspicion.

(1) Temperature measurement: Acute inflammation produces fever. (2) Leukocyte count: Leukocytes, particularly neutrophils, increase in acute inflammation. This results in a higher-than-normal percentage of immature neutrophils circulating in the blood. (3) Erythrocyte sedimentation rate: It increases during acute inflammation

Eosinophils

(appear 2 to 3 hrs after neutrophils, their granules contain a lysosomal protein highly toxic to large parasitic worms. Also, involved in allergic reaction.)

Neutrophils

(first cells to appear at the site of acute inflammation; engulf bacteria through phagocytosis. The predominant phagocyte of early inflammation.)

Mast cells

(release of histamine) (produce vasoactive mediators such as prostoglandins and leukotrienes, Platelet-activating factor, Cytokines that help with tissue regeneration.) -Cellular bags of granules located in the loose connective tissues close to blood vessels ***Skin, digestive lining, and respiratory tract -Activation ***Physical injury, chemical agents, and immunologic processes ***Biologically active molecules are released --------Histamine --------Chemotactic factors

plasma protein systems: kinin system

-Primary kinin is bradykinin -Causes dilation of blood vessels, pain, smooth muscle contraction, vascular permeability, and leukocyte chemotaxis

phagocytosis

-Process by which a cell ingests and disposes of foreign material -Production of adhesion molecules -Margination (pavementing) ------Adherence of leukocytes to endothelial cells ------Hence, the phagocyte's role begins when the inflammatory response causes it to stick avidly to capillary walls in a process called margination. -Diapedesis -------Emigration of cells through the endothelial junctions

vascular stage

-Prostaglandins and leukotrienes affect blood vessels. -Arterioles and venules dilate (vasodilation). -----*Increasing blood flow to injured area -----*Redness and warmth result -Capillaries become more permeable. -----*Allowing exudate (leakage of proteinaceous fluid) to escape into the tissues -----*Swelling and pain result

repair

-Replacement of destroyed tissue with scar tissue -Scar tissue --------Composed primarily of collagen to restore the tensile strength of the tissue

cardinal signs of inflammation

-Rubor (redness) -Tumor (swelling) -Calor (heat) -Dolor (pain) -Functio laesa (loss of function) -(The first 4 are due to increase blood flow.)

margination(pavementing)

-Adherence of leukocytes to endothelial cells -Hence, the phagocyte's role begins when the inflammatory response causes it to stick avidly to capillary walls in a process called margination.

vascular response

-Blood vessel dilation: vasodilation increases the blood flow to injured site -Increased vascular permeability and leakage of fluid out of the vessel, hence edema. Increase blood flow & inc. concentration of RBC causes warmth & redness. -White blood cell adherence to the inner walls of the vessels and migration through the vessels

plasma protein systems: coagulation (clotting) system

-Forms a fibrinous meshwork at an injured or inflamed site ***Prevents the spread of infection ***Keeps microorganisms and foreign bodies at the site of greatest inflammatory cell activity ***Forms a clot that stops bleeding ***Provides a framework for repair and healing -Main substance is an insoluble protein called fibrin

leukotrienes

-product of arachidonic acid from mast cell membranes. -similar effects to histamine in later stages

monocyte and macrophages

-type of phagocyte -Monocytes are produced in the bone marrow, enter the circulation, and migrate to the inflammatory site, where they develop into macrophages -Macrophages typically arrive at the inflammatory site 24 hours or later after neutrophils

debridement

cleaning up the dissolved clots, microorganisms, erythrocytes, and dead tissue cells

plasma protein systems: protein systems consists of

complement system, coagulation system, and kinin system

What mechanism causes the redness (erythema) associated with the inflammatory process? a)Prostaglandins b)Leukotrienes c)Arachidonic acid d)All of the above e)a and b

e) a and b -Prostaglandins and leukotrienes cause vasodilation, which brings more blood to the injured/affected area. -The symptoms caused by this vasodilation are redness/erythema and warmth.

systemic manifestations of inflammation include:

fever, leukocytosis, increased plasma protein synthesis

chronic inflammation

inflammation lasting 2 weeks or longer; often related to an unsuccessful acute inflammatory response

resolution

returning injured tissue to the original structure and function

Basophils

(precursors of mast cells)

primary intention

wounds that heal under conditions of minimal tissue loss

secondary intention

wounds that require a great deal more tissue replacement ----open wound

Mast cell synthesis of Mediators

leukotrienes. prostaglandins. platelet-activating factor.

inflammation

an automatic response to cell injury that: -Is meant to minimize the effects of injury or infection -Neutralizes harmful agents -Removes dead tissue -Generate new tissue -E.g. cellulitis (-itis)

leukocytes

increased numbers of circulating leukocytes

Now, knowing your patient has sustained a severe ankle sprain as well as cuts in the surrounding area, discuss the clinical and cellular components of his or her symptoms (redness, heat, swelling, pain, loss of function).

-Tissue damage (cellular injury) has occurred at the site of your patient's ankle. -This injury causes vasodilation and increased capillary permeability because of histamine release from degranulating mast cells. -The result is heat, swelling, and redness of the ankle. -The resulting edema is nature's splint, reducing the motion of the ankle and creating a loss of function. -Pain is due to the synthesis of prostaglandins, a type of inflammatory chemical mediator. -As inflammation progresses, neutrophils arrive to begin to clean up the debris of cellular injury. -These are followed by other granulocytes. -The plasma protein systems have also been activated, stopping any bleeding and destroying any pathogens that may have invaded the area through the break in the skin. -Cytokines and chemokines are the messengers that coordinate the entire process. -Finally, healing will occur through the action of fibroblasts and other cells that allow the wounds (internal and external) to fill in, seal, and shrink, restoring tissue integrity. -Remember that repaired tissue never regains 100% of its original tensile strength, which explains why your patient may complain of a "bad ankle that acts up sometimes" for years into the future.

plasma protein systems: complement system

-can destroy pathogens directly -activates or collaborates with every other component of the inflammatory response

fever

-caused by exogenous and endogenous pyrogens -act directly on the hypothalamus

cellular mediators of inflammation

-cellular components ***Granulocytes, platelets, monocytes, and lymphocytes

platelet-activating factor

-similar effect to leukotrienes and platelet activation

prostaglandins

-similar effects to leukotrienes; they also induce pain

H1 receptor

-type of Histamine receptor -Proinflammatory -Present in smooth muscle cells of the bronchi

interleukins

-type of cytokine -Produced primarily by macrophages and lymphocytes in response to a pathogen or stimulation by other products of inflammation -Many types -Examples :IL-1 is a proinflammatory cytokine; IL-10 is an anti-inflammatory cytokine

interferon

-type of cytokine -Protects against viral infections -Produced and released by virally infected host cells in response to viral double-stranded RNA -Types -------IFN-alpha and IFN-beta -------------*Induce production of antiviral proteins -------IFN-gamma -------------*Increases microbiocidal activity of macrophages

tumor necrosis factor-alpha

-type of cytokine -Secreted by macrophages in response to PAMP and toll-like receptor recognition ---------Induces fever by acting as an endogenous pyrogen ---------Increases synthesis of inflammatory serum proteins ---------Causes muscle wasting (cachexia) and intravascular thrombosis

hemorrhagic exudate

-type of exudative fluid -exudate contains blood: indicates bleeding

purulent exudate

-type of exudative fluid -pus: indicates a bacterial infection

fibrinous exudate

-type of exudative fluid -thick, clotted exudate: indicates more advanced inflammation

serous exudate

-type of exudative fluid -water exudate: indicates early inflammation

H2 receptor

-type of histamine receptor -Anti-inflammatory -Present on parietal cells of the stomach mucosa ***Induces the secretion of gastric acid

neutrophils

-type of phagocyte -Also referred to as polymorphonuclear neutrophils (PMNs) -Predominate in early inflammatory responses -Ingest bacteria, dead cells, and cellular debris -Cells are short lived and become a component of the purulent exudate

platelets

-type of phagocyte -activation results in degranulation and interaction with components of the coagulation system

natural killer (NK) cells

-type of phagocyte -function is to recognize and eliminate cells infected with viruses and some function in eliminating cancer cells

eosinophils

-type of phagocyte -mildy phagocytic -duties: defense against parasites and regulation of vascular mediators

acute inflammation consists of

-vascular events -cellular events -"mediators"

diapedesis

Emigration of cells through the endothelial junctions

WBCs involved in inflammation

Granulocytes (neutrophils, eosinophils, basophils, mast cells) Monocytes (monocytes ->macrophages)

Inflammation Sequence of Events

Normal Histology -> Vasodilation (at the level of postcapillary venules)-> Increased vascular permeablity (partly due to the vasodilation)-> Leakage of exudate (into the intracellular spaces)-> Margination, Rolling, Adhesion (of neutrophils)-> Transmigration (Diapedesis [or transmigrate thru the wall} of neutrophils)-> Chemotaxis (neutrophils attracted to areas outside of the blood vessel wall)-> PMN activation (to release all of the substances in their lysosomes) -> Phagocytosis: Recognition, Attachment, Engulfment, Killing (degradation or digestion)-> Termination-> 100 % Resolution, Scar, or Chronic Inflammation are the three possible outcomes

Histamine

Receptors H1 and H2

increased plasma protein synthesis

acute-phase reactant ----C-reactive protein, fibrinogen, haptoglobin, amyloid, ceruloplasmin, etc.

healing

filling in the wound; sealing the wound (epithelialization); shrinking the wound (contraction)