Pathophysiology Ch 02 Inflammation-V2

7/27/2019 Pathophysiology Ch 02 Inflammation-V2

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LEARNINGOBJECTIVES

After study ing this c hapter, the student is expected to:

1. Explain the role of normal defences in preventing disease.

2. Describe how changes in capillary exchange affect the tissues and the blood.

3. Compare normal capillary exchange with exchange during the inflammatory response.

4. Describe the local and systemic effects of inflammation.

5. Explain the effects of chronic inflammation.

6. Discuss the modes of treatment of inflammation.

7. Describe the types of healing and complications of healing.

8. List the factors , including a specific example for each, that hasten healing.

9. Identify the classifications of burns and describe the effects of burns.

10. Describe the possible complication occurring in the first few days after a burn.

11. Explain the reasons why the healing of a burn may be difficult.

Chapter 2: Inflammation & Healing


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in f lamm ation isa protective non-specific

response intended to eliminate the initial cause

of cell injury as well as the necrotic cells and

tissues resulting from the original insult.

Inflammations are named using the ending -itis.

For example, pancreatitis, appendicitis,

laryngitis or ileitis.

Inflammation is interwoven with repair

processes.

Inflammation may be classified into two types:

Acute inflammationis of relatively shortduration, lasting from a few minutes up to a few

days, and is characterized by fluid and plasma

protein exudationand a predominantly

neutrophilic leukocyte accumulation.

Chronic inflammationis of longer duration

(days to years) and is typified by influx of

lymphocytes and macrophageswithassociated vascular proliferationand

scarring.

Acute inflammation

Major phenomena (events):

1- Vascular ch anges: After transient (seconds)

vasoconstriction, arteriolarvasodi lat ion

occurs > redness (eryth ema) and warmth.

the microvasculature becomes morepermeable, resulting in the movement of

protein-rich fluid into the extravascular

tissues. increasing blood viscosityand

slowing the circulation. These changes are

reflected microscopically by numerous dilated

small vessels packed with erythrocytes

(stasis).N.B. .Inflammatory fluidexudateis protein-rich

fluid that contain inflammatory cells, while

transudationis filtration of plasma with low

protein content.

2- Cellular events :emigration of the leukocytes

(neutrophils) from the microcirculation and

accumulation in the focus of injury (cellular

recruitment and activation). It involves

leukocyte margination, rolling, adhesion to the

endothelial surface and then transmigration

(diapedesis).


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Inflammatory Mediators:

ECs = endothelial cells


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Local Effects

The cardinal signs of inflammation are redness

(rubor or erythema), heat, swelling, pain andloss of function.

Redness and warmth are caused by increased

blood flow into the damaged area.

Swelling or edema is caused by the shift of

protein and fluid into the interstitial space. Painresults from the increased pressure of

fluid on the nerves, especially in enclosed

areas, and by the local irritation of nerves by

chemical mediators.

Loss of function may develop if the cells lack

nutrients, for example, liver cells, or ifswelling interferes mechanically with an

action, for example, joint movement.

SYSTEMIC EFFECTS

(acute-phase reaction)

Fever, increased somnolence, malaise,

anorexia, accelerated degradation ofskeletal muscle proteins, hypotension,

hepatic synthesis of a variety of

proteins (e.g., complement and

coagulation proteins), and alterations

in the circulating white blood cell pool.

Fever results from the release of

pyrogens, or fever-producing

substances (e.g., interleukin-l), from white

blood cells (WBCs) or macrophages.

Pyrogens circulate in the blood and cause

the body temperature control system

(the thermostat) in the hypothalamusto

be reset at a higher level.


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Leukocytosis(increased white blood cell count). The leukocyte count typically increases to 15,000or 20,000 cells per L (normal = 4000 to 10,000 cells per L) but may climb as high as 40,000 to100,000 cells per L, a so-called leukemoid reaction. Leukocytosis initially results from the releaseof cells from the bone marrow and is associated with an increased number of relatively immature

neutrophils in the blood ("left-shift"). Most bacterial infections induce a relatively selective increase in polymorphonuclear cells

(neutrophilia)

Parasitic infections (as well as allergic responses) characteristically induce eosinophilia.

Certain viruses, such as infectious mononucleosis, mumps, and rubella, engender selectiveincreases in lymphocytes (lymphocytosis).

However, most viral infections, as well as rickettsial, protozoal, and certain types of bacterial

infections (typhoid fever), are associated with a decreased number of circulating white cells(leukopenia). Leukopenia is also encountered in infections that overwhelm patients debilitated by,for example, disseminated cancer.

Elevated serum C-reactive protein (CRP), an elevated erythrocyte sedimentation rate or

ESR, and increased plasma proteins and cell enzymes in the serum are nonspecific Changes

Increased circulating plasma proteins (fibrinogen, prothrombin, and alpha-antitrypsin).

Cell enzymes and isoenzymes (more specific forms) may be elevated in the blood in the presence

of severe inflammation and necrosis. For example, aspartate aminotransferase (AST, formerlyserum glutamicoxaloacetic transaminase [SGOT]) is elevated in liver disease and in the acute stage

of a myocardial infarction (heart attack). However, the isoenzyme CK-MB(isoenzyme of creatine

kinase with myocardial component) is specific for myocardial infarction. The enzyme alanine

aminotransferase (ALT) is specific for the liver.

Laboratory Findings / Diagnostic tests


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Outcomes of Acute Inflammation

Resolut ion.When the injury is limited or short-lived, when there has been no or minimal

tissue damage, and when the tissue is capable of replacing any irreversibly injured cells, theusual outcome is restoration to histologic and functional normalcy. lymphatic drainage andmacrophage ingestion of necrotic debris lead to the clearance

Scarr ingor f ibrosisresults after substantial tissue destruction or when inflammation occursin tissues that do not regenerate.. Abscessformationmay occur in the setting of extensive

neutrophilic infiltrates (see later) or in certain bacterial or fungal infections (these organismsare then said to be pyogenic, or "pus forming"). Due to the extensive underlying tissuedestruction (including the extracellular matrix), the only outcome of abscess formation isscarring.

Progression to c hronic inf lammat ionmay follow acute inflammation, Depending on theextent of the initial and ongoing tissue injury, as well as the capacity of the affected tissues toregrow, chronic inflammation may be followed by regeneration of normal structure andfunction (regenerat ion) or may lead to scarring.


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Chronic Inflammation

Chronic inf lammat ion is characterized by the following:

prolonged duration (weeks to months to years) .

Infiltration with mononuclear ("chronic inflammatory") cells, including macrophages,

lymphocytes, and plasma cells.. Tissue destruction, largely directed by the inflammatory cells.

Granuloma formation. A mass of inflammatory cells with necrotic center and surrounded by

fibroblasts and collagen.

Repair, involving new vessel proliferation (angiogenesis) and fibrosis.


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MORPHOLOGIC PATTERNS OF ACUTE AND CHRONIC INFLAMMATION

1- SEROUS INFLAMMATION. This is

characterized by watery, relatively protein-

poor fluid (effusion).

The skin blister resulting from a burn or

viral infection is a good example of a

serous effusion accumulated either within

or immediately beneath the epidermis of

the skin.

2- FIBRINOUS INFLAMMATION.

severe injuries > vascular permeability allowing

fibrinogen to pass the endothelial barrier >

eosinophilic meshwork of threads or amorphouscoagulum

Fate: 1- Resolution. Fibrinous exudates may be

degraded by fibrinolysis, and the accumulated

debris may be removed by macrophages,

resulting in restoration of the normal tissue

structure.

2- Organization. failure to completely remove the

fibrin results in the ingrowth of fibroblasts and

blood vessels > scarring > interfere with function.


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3- SUPPURATIVE (PURULENT) INFLAMMATION.

Purulent exudate (pus)consisting of neutrophils,

necrotic cells, and edema fluid. Certain organisms (e.g.,

staphylococci) are more likely to induce this localized

suppuration and are therefore referred to as pyogenic.

Abscessesare localized collections of pus that may becaused by deep seeding of pyogenic organisms into a

tissue or by secondary infections of necrotic foci.

Abscesses typically have a central, largely necrotic

region rimmed by a layer of preserved neutrophils with

a surrounding zone of dilated vessels and fibroblastic

proliferation indicative of early repair.

Cellulitisis a diffuse form of suppurative inflammation.

4- ULCERATION.

site of inflammation where an epithelial surface has

become necrotic and eroded (lost), with associated

subepithelial acute and chronic inflammation.


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TREATMENT OF INFLAMMATION

1- Drugs

O O


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TREATMENT OF INFLAMMATION

2- Other Therapies

First-aid directives for injury-related inflammation frequently recommend Rest, Ice,

Compression, Elevation (RICE).

Cold applications are useful in the early stage of acute inflammation. Application of cold

causes local vasoconstriction, thereby decreasing edema and pain. The use of hot or cold

applications during long-term therapy and recovery periods depends on the particular

situation. In some instances, for example, acute rheumatoid arthr i t is, heat, and moderate

activity may improve the circulation in the affected area, thereby removing excess fluid, pain-

causing chemical mediators, and waste metabolites as well as promoting healing.

Mild-to-moderate exercise is useful in cases of many chronic inflammatory conditions

where improved blood and fluid flow is beneficial and mobility could be improved.

Other treatment measures, including physiotherapy, may be necessary to maintain joint

mobility, although splintsmay be required during acute episodes to prevent contractures,fixed abnormal joint positions.

Rest and adequate nutrition and hydration are important.

Healing


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HealingRepair begins very early in the process of inflammation and involves two processes:

1- Regeneration:Replacement of injured tissue by parenchymal cells of the same type.

2- Fibrosis:Replacement of injured tissue by connective tissue resulting in a scar.

Healing BY FIBROSIS

Repair begins within 24 hours of injury by the migration of

fibroblasts and the induction of fibroblast and

endothelial cell proliferation. By 3 to 5 days,

granulat ion tissue, is apparent. It is characterized by

prol i ferat ion of f ibro blasts and new th in-walled,

delicate capillaries, in a loose extracellular matrix.

Granulation tissue then progressively accumulates

connective tissue matrix, eventually resulting in densef ibrosis (scarring), which may further remodel over

time.

WOUND HEALING involves the following steps:

Induction of an acute inflammatory response by theinitial injury

Parenchymal cell regeneration (where possible)

Migration and proliferation of both parenchymal and

connective tissue cells

Synthesis of ECM proteins

Remodeling of parenchymal elements to restore tissue

function Remodeling of connective tissue to achieve wound

strength


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Healing by First Intention

(primary union)

Healing of a clean, uninfected surgical incision approximated by surgical sutures so epithelial

regeneration predominates over fibrosis. The narrow incisional space rapidly fills with fibrin-

clotted blood; dehydration at the surface produces a scabto cover and protect the healingrepair site.

Within 24 hours, neutrophilsare seen at the incision margin, migrating toward the fibrin

clot. Within 24 to 48 hours, epithelial cells from both edges have begun to migrate and

proliferate along the dermis to meet in the midline.

By day 3, neutrophils have been largely replaced by macrophages, and granulat ion t issu e

progressively invades the incision space.

By day 5,neovascularization reaches its peak as granulation tissue fills the incisional space.

Collagen f ibr i lsbecome more abundant and begin to bridge the incision. The epidermis

recoversits normal thickness

Dur ing the second w eek, there is continued collagen accumulation and fibroblast

proliferation. The leukocyte infiltrate, edema, and increased vascularity are substantially

diminished. The long process of "blanching" begins.

By the end of the f i rst mon th, the scar comprises a cellular connective tissue largely devoidof inflammatory cells and covered by an essentially normal epidermis. However, the dermal

appendagesdestroyed in the line of the incision are permanently lost.

S d i (h li b d i t ti )


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Secondary union, (healing by second intention)

Secondary healing differs from

primary healing by:

1- Greater volume of necrotic

debris, exudate, and fibrin that must

be removed. Inflammatory reaction

is more intense, with greater

potential for secondary,

inflammation-mediated injury.

2- A greater volume of granulation

tissue results in a greater mass of

scar tissue.3- Secondary healing exhibits the

phenomenon of wound

contractiondue to the presence of

myofibroblasts (modified

fibroblasts with contractile

function).

Causes of delayed Healing:


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y g

1- Infectionis the single most important cause of delay in healing.

2- Nutritionhas profound effects on wound healing; protein deficiency, and vitamin C deficiency, inhibitcollagen synthesis.

3- Glucocorticoids (steroids)have anti-inflammatory effects, and their administration may result in poorwound strength owing to diminished fibrosis. Chemotherapy also delays healing.

4- Mechanical factorssuch as increased local pressure or torsion may cause wounds to pull apart.

5- Poor perfusion, due to arteriosclerosis, or obstructed venous drainage.

6- Foreign bodies: fragments of steel, glass, or even bone.

7- The type (and volume) of tissue and The location of the injury, For example, inflammations arising intissue spaces (e.g., pleural) develop extensive exudates > resolution or organization.

9-Advanced age, anemia, diabetes, cancer.


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Complications of wound healing:

1- Loss of Funct ion: results from the loss of normal cells and the lack of specialized structures or

normal organization in scar tissue. For example, skin, organized organ such as the kidney

2- Contractures and Obstruc t ions : Scar tissue is non elastic and tends to shrink over time. Thisprocess may restrict the range of movement of a joint and eventually may result in fixation and

deformity of the joint, a condition known as contracture. Fibrous tissue may also limit movement of

the mouth or eyelids. Physiotherapyor surgerymay be necessary to break down the fibrous tissue

and improve mobility. If the esophagus is shortened, malposition of the stomach (hiatal hernia) or a

narrowed esophagus (stenosis) causing obstruction during swallowing.

3- Adhesion s: are bands of scar tissue joining two surfaces that are normally separated. Common

examples are adhesions between loops of intestine (see Fig. 2-88) or between the pleural

membranes.


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4- Hypertrophic scar tissue.An overgrowth of fibrous tissue consisting of excessive collage

deposits may develop, leading to hard ridges of scar tissue or keloid formation. These masse

are disfiguring and frequently cause more severe contractures.Keloid. This is accumulation of exuberant amounts of collagen that gives rise to prominent, raised scarsThere appears to be a heritable predisposition to keloid formation, and the condition is more common in

blacks.

5- Ulceration. Blood supply may be impaired around the scar, resulting in further tissue breakdown and

ulceration at a future time. This may occur when scar tissue develops in the stomach following surgery

or healing of an ulcer.


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Acute Inflammation http://www.youtube.com/watch?v=suCKm97yvyk&feature=related
http://www.youtube.com/watch?v=suCKm97yvyk&feature=relatedhttp://www.youtube.com/watch?v=suCKm97yvyk&feature=relatedhttp://www.youtube.com/watch?v=suCKm97yvyk&feature=relatedhttp://www.youtube.com/watch?v=suCKm97yvyk&feature=related


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p y y y

Wound Healing http://www.youtube.com/watch?v=FraKUUetOpc&feature=related
http://www.youtube.com/watch?v=suCKm97yvyk&feature=relatedhttp://www.youtube.com/watch?v=FraKUUetOpc&feature=relatedhttp://www.youtube.com/watch?v=FraKUUetOpc&feature=relatedhttp://www.youtube.com/watch?v=suCKm97yvyk&feature=relatedhttp://www.youtube.com/watch?v=suCKm97yvyk&feature=relatedhttp://www.youtube.com/watch?v=suCKm97yvyk&feature=related

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Pathophysiology Ch 02 Inflammation-V2

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