lecture 8 inflammation, tissue repair and wound healing

acute inflammation(short)

• infiltration of neutrophils

• exudation of fluid

chronic inflammation (long)

• infiltration of macrophages and lymphocytes

• proliferation of blood vessels, fibrosis and tissue necrosis

neutrophils (acute)

first responder at site of inflammation

• predominate in early inflammatory responses

Neutrophil count in blood increases during acute inflammation, especially in bacterial infections and tissue injury= leukocytosis

• with excessive demand for phagocytes, immature forms of neutrophils(bands) are released from bone marrow= left shift

monocytes/macrophages (acute)

arrive at inflammatory site shortly after neutrophils and become macrophages

• produce vasoactive mediators that promote tissue regeneration

• engulf lager and greater quantities of foreign material

aid in activating adaptive immune system

• contribute to initiation of healing and wound repair

important role in chronic inflammation

eosinophils

help contro vascular effects of inflammation due to mast cell degranulation

basophils

blue granules contain histamine and heparin

• contribute to inflammatory respond in allergic reactions

acute inflammation phases

1. vascular phase

• vasodilation + increase permeability

(more blood + leaky vessels + fluid buildup → redness, heat, swelling, pain)

2. cellular phase

• migration of leukocytes(WBCs) to site of injury

• leukocyte activation→ phagocytosis

vasodilation

blood vessels widen

• area becomes congested (increase blood flow)

• slower blood velocity

increased capillary permeability

blood vessels become leaky

• blood vessels become porous from contraction of endothelial cells→ protein-rich fluid leaks into injured tissue(exudation)→ swelling (edema)

• loss of fluid→increased concentration of blood cells (RBCs, WBCs, platelets and clotting factors) more viscous→ redness(erythema) and warmth

localizes spread of infectious microorganisms

• stimulation of nerve endings→ pain and impaired function

due to pressure exerted by exudate accumulations

cellular phase

Movement of phagocytic leukocytes into site of injury

1. leukocyte margination/pavementing (edges)

2. leukocyte rolling and adhesion to endothelium (stick)

3. trasmigration across endothelium and diapedesis (squeeze

4. chemotaxis (chemical signals)

5. activation and phagocytosis

leukocyte extravasation 1

This is how white blood cells leave the blood and go into tissues

1. leukocytes accumulate along vessel wall

leukocyte adherence= margination/pavementing

2. leukocytes move along periphery(edge) of blood vessels

release of cytokines→ expression of cell adhesion molecules(selectins) on endothelial cells that bind to carbohydrate receptors on leukocyte surface

• slows leukocyte flow to move along endothelial surface with a rolling movement

leukocyte extravasation

3. diapedesis=transmigration (This is when white blood cells leave the blood vessel)

4. Chemotaxis

• leukocytes wanter through tissue guided by chemical gradient of chemoattractants

• chemokines (special signaling chemicals that attract WBCs)

• cytokines that direct trafficking of leukocytes

phagocytosis steps

1. recognition and adherence to pathogen

• WBC recognizes and sticks to the pathogen

• Opsonization = pathogen is “tagged” (easier to recognize and grab)

2. engulfment- Pseudopods surround and enclose pathogen in phagosome and fuses with lysosome → phagolysosome

3. destruction of pathogen- uses ROS, H₂O₂

cytokines

TNF-α and IL-1

• Proinflammatory effects

• Endothelial cell activation

• Express adhesion molecules, release cytokines and ROS

• Mediators of acute-phase responses (fever, immune system

serous exudates

watery fluids low in protein content

• e.g skin blisters

hemmorhagic exudates

occur when there is severe tissue injury that causes damage to blood vessels or when there is significant leakage of RBCs from capillaries

fibrinous exudates

results from increased vascular permeability(blood vessel walls), allowing large proteins(fibrinogen) to leak out of vessels into tissues

• form a thick and sticky meshwork (fibrinogen causes RBC polymerization)

• e.g. bacterial pneumonia

purulent or suppurative exudates

formation of pus (suppuration)

• composed of large number of degraded neutrophils, cellular debris and edema fluid

• e,g, abscess

nonspecific chronic inflammation

involves a diffuse accumulation of macrophages and lymphocytes (lymphocytosis) at site of injury

• ongoing chemotaxis causes macrophages to infiltrative inflamed site

granulomatous inflammation

protective cellular response to contain a harmful agent that is difficult to eradicate or indigestible material during acute inflammatory response

• nodular mass of macrophages surrounded by lymphocytes=granuloma

• activated macrophages= epithelioid cells( resemble epithelial cells)

• encapsulated by collagen

• associated with foreign bodies(splinters,sutures)+infections(tuberculosis)

tissue repair and wound healing phases

1. inflammatory phase

2. proliferative phase

3. remodeling phase

inflammatory phase

acute inflammatory response:

• hemostasis/coagulation- formation of blood clot

• vascular phase of inflammation

• cellular phase of inflammation- migration of phagocytic WBCs

after 24hrs macrophages arrive- engulf, digest and remove cell debris

(stop bleeding → bring WBCs → clean up damage)

proliferative phase

• Macrophages- Recruit fibroblasts, Stimulate epithelial cell growth, Stimulate vascular endothelial cells → angiogenesis

• Fibroblasts- Synthesize and secrete collagen to fill in gaps

• Granulation tissue- Red, granular, fragile connective tissue

• Fibrogenesis- •nflux of activated fibroblasts+ Secretion of ECM components (fibronectin, hyaluronic acid, proteoglycans and collagen)

(build new tissue + new blood vessels + fill wound with collagen)

remodeling phase

as healing progresses, number of proliferating fibroblasts and new vells decreases

• transformation of highly vascular granulation tissue into a pale, large avascular scare

primary intention

small clean wound

• wound edges line up/close together

• minimal tissue loss

• ex: sutured surgical incision, paper cut

secondary intention

great loss of tissue with contamination

• larger, open, craterlike wounds

• healing is slower

• ex: burns and large surface wounds