Unit II: the inflammatory response

The body’s __________ & __________ response
to cell injury intended to eliminate the cause of
the injury, remove damaged tissue, and generate
new tissue

physiologic and pathologic

What are the five cardinal signs of inflammation?

• redness (erythema)

• swelling (edema)

• warmth (hyperthermia)

• pain

• loss of function

What is the:

• Response of the host to injury within minutes to hours. May be triggered by infections, immune reactions, trauma, physical or chemical agents, and tissue necrosis.

• This kind of inflammation is self-limited and has a short duration

acute inflammation

Cells of inflammation, identify this cell:

Single-cell thick, selectively permeable lining of blood vessels; regulate leukocyte movement, synthesize inflammatory mediators, and participate in repair

• Role in inflammation:

  • Provide selectively permeable barrier to stimuli

  • Regulate leukocyte movement out of the vessel wall to the
    site of injury

  • Synthesize and release inflammatory mediators

  • Secrete colony stimulating factors (CSFs) to regulate
    immune cell proliferation

  • Participate in the repair process in inflammation

endothelial cells

Cells of inflammation, identify this cell:

• Cellular mechanisms of hemostasis

• Release over 300 proteins when activated- a significant number
  of these are inflammatory mediators

• clot

platelets

Cells of inflammation, identify this cell:

• First responders to the site of inflammation;

• destroy engulfed microbes and dead tissue;

• immature neutrophils are called "bands"

• count of this cell increases greatly during inflammation, especially w/ bacterial infections

• high count of this cell= bacterial infection

neutrophils

Cells of inflammation, identify this cell:

• Largest leukocytes

• arrive shortly after neutrophils

• sustain phagocytosis for several days

• play a role in chronic inflammation

• help resolve inflammatory process

• produce potent vasoactive, inflammatory mediators

monocytes/macrophages

Cells of inflammation, identify this cell:

• Increase during allergic reactions and parasitic infections

• Control the release of certain chemical mediators

eosinophils

Cells of inflammation, identify this cell:

• Contain histamine and other vasoactive mediators

basophils

Cells of inflammation, identify this cell:

• Release inflammatory mediators, including histamine, cytokines,
  and interleukins

mast cells

Stages of inflammation:

1. vascular stage: small vessel changes at the site of injury leading to tissue edema

2. cellular stage: changes in the endothelial cells lining the blood vessels and the movement of phagocytic leukocytes in the area

What best fits the description of the vascular stage of inflammation?

1. Very brief vasoconstriction of arteries.
   
   

2. Inflammatory mediators, such as histamine, induce vasodilation immediately following the brief vasoconstriction.

3. Vasodilation results in the opening of the capillary beds in the affected area, leading to “congestion” of this area. Leads to erythema and warmth.

4. Inflammatory mediators cause increased capillary permeability following vasodilation, causing “leaking” of exudate (fluid) into the extravascular spaces. This concentrates important cells of inflammation and keeps any microorganisms local.

5. Increased capillary permeability leads to a loss of plasma proteins. This decreases intracapillary osmotic pressure, causing fluid to leak into tissues and produce the edema (swelling), pain, and impaired function. The extra fluid in the tissues dilutes the offending agent

What description best fits the cellular stage of inflammation?

1. Margination and adhesion to the endothelium- Leukocytes accumulate and migrate to the injured area, adhering to the endothelium at the site of injury.

2. Transmigration across the endothelium- The adhesion of leukocytes to the endothelium causes the endothelial cells to separate, allowing the leukocytes to pass through the vessel wall
   (or transmigrate through) and then migrate to tissue spaces.

3. Chemotaxis- Directed cell migration. Chemicals, proteins, and cellular debris secrete substances that guide the leukocytes through the tissues to the site of injury/infection.

4. Activation and phagocytosis- Monocytes, neutrophils, and tissue macrophages are activated to perform phagocytosis.

What is margination and adhesion

Leukocytes accumulate and adhere to the endothelium at the site of injury

What is transmigration?

adhesion of leukocytes to the endothelium causes the endothelial cells to separate, allowing the leukocytes to pass through the vessel wall (or transmigrate through) and then migrate to tissue spaces.

What is chemotaxis?

Directed cell migration; chemicals, proteins, and
cellular debris secrete substances that guide the leukocytes through the tissues to the site of injury/infection.

What are inflammatory mediators ?

Chemical substances that produce the signs and symptoms of
inflammation

• Classified by function

  • histamine

  • Arachidonic Acid
    Metabolites

  • Platelet-Activating
    Factor

  • plasma proteins

  • cytokines and chemokines

  • nitric oxide and oxygen-dervied free radicals
    

Inflammatory mediators:

HISTAMINE

• Present and preformed in cells

• Among the first mediators to be released during acute inflammatory reactions

• *Causes dilation of arterioles and increases capillary permeability of venules

• Binds to histamine receptors on endothelial cell

Local(certain part/area) Manifestations of Inflammation

a. Five cardinal signs of inflammation

• b. Manifestations range from swelling and exudates to abscess formation or ulceration

  • c. Exudates

    • i. Serous

    • ii. Hemorrhagic (sanguineous)
      iii. Fibrinous
      iv. Membranous or pseudomembranous
      v. Purulent or suppurative

• d. Abscess formation: Localized area of inflammation containing purulent exudate
  that has been “walled off” by fibroblasts.

• e. Ulceration: Site of inflammation where the epithelial surface (skin, GI tract, etc.) has become necrotic and eroded. May be due to trauma or vascular insufficiency

serous exudate

Type of inflammatory exudate:

• clear,

• watery,

• made of plasma and has low protein levels (part of normal wound healing)

Hemorrhagic (sanguineous) exudate

type of inflamatory exudate:

• bloody drainage

• blood vessels ruptured during cellular injury

Fibrinous exudate

Type of inflammatory exudate:

• thick

• sticky

• rich in fibrinogen

Membranous or pseudomembranous exudate

Type of inflammatory exudate:

• necrotic cells

• purulent drainage

Purulent (suppurative) exudate

• Pus-containing type of inflammatory exudate

• indicates infection

  • it has:

  • WBCs

  • dead tissue,

  • cellular debris

  • bacteria

• foul odor

Abcess formation

Localized area of inflammation containing purulent exudate
that has been “walled off” by fibroblasts

What is an ulceration?

Site of inflammation where the epithelial surface (skin, GI tract, etc.) has become necrotic and eroded. May be due to trauma or vascular insufficiency.

• local manefestation

Systemic manefestations of inflammation

• acute phase response

• WBC response

• lymphadenitis

ACUTE PHASE RESPONSE(how long it takes to come):

Systemic manefestation of inflammation:

i. Hours or days of onset of inflammation or infection
ii. Generated by the release of cytokines which affect the thermoregulatory
center in the hypothalamus to produce a fever

iii. Production of neutrophils in the bone marrow is stimulated

iv. Other manifestations due to cytokine effects on the central nervoussystem:

• fever,

  • older adults dont ofter present w/ fever , first manefestation is confusion(delerium)

• anorexia,

• somnolence(extreme drowsiness),

• malaise(feeling bad)

v. C-reactive protein (CRP) is a protein produced by the liver in the acute phase response and is an important biomarker for inflammation. May be protective

a protein produced by the liver in the acute
phase response and is an important biomarker for inflammation. May be protective

c-reactive protein (CRP)

White Blood Cell (WBC) Response

Systemic manefestation of inflammation:

i. Production of leukocytes increases with inflammation, especially from bacterial infection
ii. Normal WBC count: 4,000 - 10,000
iii. Different WBC increase in response to different problems (Example- Bacterial infections → Rise in neutrophils / Parasitic infections → Rise in eosinophils

What is the normal WBC count?

4,000 - 10,000

Lymphadenitis

Systemic Manifestation of Inflammation:

i. Reaction in the lymph nodes that drains the affected area
ii. Lymph node(s) may become swollen and palpable
iii. Painful, palpable lymph nodes: infection
iv. Nonpainful lymph nodes = cancer

What do mean painful, palpable lymph nodes mean?

infection

What do nonpainful lymph nodes mean?

cancer

Chronic inflammation

• a. Self-perpetuating and long-lasting (weeks to years)

• b. May result from recurrent or progressive acute inflammation or from low-grade responses to inflammation that fail to initiate an acute response

  • i. Low-grade or persistent infections or irritants that are unable to penetrate
    deeply or spread rapidly

  • ii. May be caused by foreign bodies: Examples – talc, silica, asbestos, or surgical materials.

  • iii. May be caused by viruses, bacteria, fungi, or parasites

• c. Macrophages and Lymphocytes are the cells involved

• d. Risk of scarring and deformity is higher

• e. Two types:

  • Nonspecific Chronic Inflammation , thickening and scarring

  • Granulomatous Inflammation