acute and chronic inflammation

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Acute and Chronic Inflammation

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Page 1: Acute and chronic inflammation

Acute and Chronic Inflammation

Page 2: Acute and chronic inflammation

Referrence Chapter 2, “Acute and Chronic

Inflammation” in Robbins’ Basic Pathology, pages 31-57

Page 3: Acute and chronic inflammation

Introduction Inflammation is a defensive host

response to foreign invaders and necrotic tissue.

Can be acute or chronic.

Page 4: Acute and chronic inflammation

Acute inflammation

Page 5: Acute and chronic inflammation

Acute inflammation Immediate and early response to

tissue injury (physical, chemical, microbiologic, etc.)

Acute inflammation has two major components : Vascular changes Cellular events

Page 6: Acute and chronic inflammation

Vascular change

Page 7: Acute and chronic inflammation

Vascular change The main vascular reactions of acute

inflammation are increased blood flow followed by vasodilation and increased vascular permeability: warmth and redness Opens microvascular beds and protein-

rich fluid moves into extravascular tissues Migration of leukocytes (principally neutrophils)

Page 8: Acute and chronic inflammation

Increased vascular permeability This will leads to the movement of

protein-rich fluid and blood cells into the extravascular tissue. The resulting protein-rich

accumulation is called an exudate. Increases interstitial osmotic pressure

contributing to edema.

Page 9: Acute and chronic inflammation
Page 10: Acute and chronic inflammation

Vascular leakage several mechanisms may contribute

to increased vascular permeablity: Endothelial cell contraction that leading

to intracellular gaps of venules This occur after binding of histamines and

bradykinins, and many other mediators and is usually short-lived (15 – 30 min.)

Page 11: Acute and chronic inflammation

Vascular leakage

Cytokine mediators (TNF, IL-1) induce endothelial cell junction retraction through cytoskeleton reorganization

This reaction may take 4 – 6 hrs to develop ,and lasting for 24 hrs or more

Page 12: Acute and chronic inflammation

Vascular leakage Endothelial injuries result in vascular

leakage by causing direct endothelial cell necrosis, detachment making them leaky until they are repaired or may cause delayed damage as in thermal, certain bacterial toxins or Ultraviolet injury.

Page 13: Acute and chronic inflammation

Vascular leakage Certain mediators such as vascular

endothelial growth factor (VEGF) may cause increased transcytosis via intracellular vesicles which travel from the luminal to basement membrane surface of the endothelial cell

All or any combination of these events may occur in response to a given stimulus

Page 14: Acute and chronic inflammation

Leukocyte cellular events

Page 15: Acute and chronic inflammation

Leukocyte cellular events Leukocytes leave the vascular lumen to

the extravascular space through the following sequence of events: Margination and rolling along the vessel wall Firm adhesion and transmigration between

endothelial cells Chemotaxis and activation

Page 16: Acute and chronic inflammation
Page 17: Acute and chronic inflammation

Margination and Rolling With increased vascular permeability, fluid

leaves the vessel causing leukocytes to settle-out of the central flow column and “marginate” along the endothelial surface

Endothelial cells and leukocytes have complementary surface adhesion molecules which briefly stick and release causing the leukocyte to roll along the endothelium until it eventually comes to a stop as mutual adhesion reaches a peak

Page 18: Acute and chronic inflammation

Margination and Rolling Early rolling adhesion mediated by

selectin family of adhesion molecules: E-selectin (on endothelium cell) P-selectin (present on platelets,

endothelium) L-selectin (on the surface of most

leukocytes)

Page 19: Acute and chronic inflammation

Adhesion The rolling leukocytes are able to sense

change on the endothelium that initiate the next step in the reaction of leukocytes, which is firm adhesion to endothelial surface

Occur as leukocytes adhere to the endothelial surface and is mediated by the interaction of integrins on leukocytes binding to IG-family adhesion proteins on the endothelium.

Page 20: Acute and chronic inflammation

Transmigration (diapedesis)

Is the movement of leukocyte across the endothelial surface

Occurs after firm adhesion and mediated by palatelete endothelial cell adhesion molecules-1 (PECAM –1)

on both leukocyte and endothelium

Page 21: Acute and chronic inflammation

Chemotaxis Leukocytes follow chemical gradient to

site of injury this process called (chemotaxis)

Chemotactic factors for neutrophils, produced at the site of injury, include: Bacterial products Components of complement system especially (C5a) Cytokines.

Page 22: Acute and chronic inflammation

Phagocytosis Phagocytosis is the ingestion of

particulate material by phagocytic cell

neutrophils and monocytes-macrophages are the most important phagocytic cells

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Phagocytosis consists of three steps: Recognition and attachment of the

particle Engulfment (form phagocytic vacuole) Killing and degradation of the

ingested materials.

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Defects of leukocyte function Defects of leukocyte adhesion:

Leukocyte adhesion deficiency type I : is associated with recurrent bacterial

infections. Leukocyte adhesion deficiency type 2 : is associated with recurrent bacterial

infections and result from mutations in the gene that required for the synthesis of sialyl-lewis X on neutrophils.

Page 25: Acute and chronic inflammation

Defects of leukocyte function Defects of

chemotaxis/phagocytosis: Microtubule assembly defect leads to

impaired locomotion and lysosomal degranulation (Chediak-Higashi Syndrome)

Page 26: Acute and chronic inflammation
Page 27: Acute and chronic inflammation

Possible outcomes of acute inflammation

Page 28: Acute and chronic inflammation

Possible outcomes of acute inflammation Complete resolution of tissue structure

and function: When the injury is limited or short-lived. There has been no or little tissue damage When the injured tissue is capable of regeneration

Scarring (fibrosis): When inflammation occur in tissues that do not

regenerate The injured tissue is filled with connective tissue

Page 29: Acute and chronic inflammation

Outcomes (cont’d) Abscess formation occurs with

some bacterial or fungal infections Progression to chronic

inflammation.

Page 30: Acute and chronic inflammation

Chronic inflammation

Page 31: Acute and chronic inflammation

Chronic inflammation Is inflammation of prolonged duration

(week to years) in which continuing inflammation, tissue injury, and healing, often by fibrosis, proceed simultaneously.

Page 32: Acute and chronic inflammation

Chronic inflammation Is characterized by a different set of

reactions: Lymphocyte, macrophage, plasma cell

(mononuclear cell) infiltration Tissue destruction by inflammatory cells Repair with fibrosis and angiogenesis

(new vessel formation)

Page 33: Acute and chronic inflammation

Chronic inflammation may arise in the following setting : Persistent injury or infection (ulcer, TB) Prolonged toxic agent exposure (silica) Autoimmune disease states (RA, SLE)

Page 34: Acute and chronic inflammation

Chronic inflammatory cells and mediators

Page 35: Acute and chronic inflammation

Chronic inflammatory cells and mediators Macrophages

The dominant cells. Scattered all over (Kupffer cells,

sinus histiocytes, alveolar macrophages, etc.

Derived from circulating blood monocytes and reach site of injury within 24 – 48 hrs and transform to macrophages.

Page 36: Acute and chronic inflammation

Chronic inflammatory cells and mediators Two majors pathways of macrophage

activation: Classical macrophage activation: induced byT cell-derived cytokines, endotoxins, and other

products of inflammation Alternative macrophage activation: induced by cytokines produced by T lymphocytes and other cell

including mast cell and eosinophils

Page 37: Acute and chronic inflammation

Chronic inflammatory cells and mediators Macrophages have several roles in host

defense and inflammatory reaction: Ingest and eliminate microbes and dead

tissue. Initiate the process of tissue repair. Secrete mediators of inflammation such

as cytokines.

Page 38: Acute and chronic inflammation

Chronic inflammatory cells and mediators Lymphocytes (T - B )

Antigen-activated (via macrophages and dendritic cells)

Lymphocytes and macrophages interact in a bidirectional way and these interaction

play an important role in propagating chronic inflammation lymphocyte release macrophage-activating cytokines (in turn, macrophages release lymphocyte-activating cytokines until inflammatory stimulus is removed)

Page 39: Acute and chronic inflammation

Chronic inflammatory cells and mediators Eosinophils

Found especially at sites of parasitic infections, and as part of immune reaction mediated by IgE

Typically associated with allergies.

Page 40: Acute and chronic inflammation

Granulomatous Inflammation

Page 41: Acute and chronic inflammation

Granulomatous Inflammation Is a distinctive pattern of chronic

inflammation characterized by aggregates of activated macrophages and scattered lymphocytes.

Page 42: Acute and chronic inflammation

Granulomatous Inflammation can form under three setting : Persistance T-cell response to certain

microbes (such as TB) In some immune mediated inflammatory

diseases (Crohn disease) In sarcoidosis disease in response to

relatively inert foreign bodies(suture or splinter)

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Systemic effects

Page 44: Acute and chronic inflammation

Systemic effects Fever

The most prominent manifestation of acute-phase response.

Fever is produced in response to pyrogens which stimulate prostoglandine synthesis.

PGE stimulate the production of neurotransmitters to reset the temperature at a higher level.

Page 45: Acute and chronic inflammation

Systemic effects (cont’d) Leukocytosis

Is a common feature of inflammatory reaction, espicially those induced by bacterial infection

Elevated white blood cell count. Other manifestations include:

Increased heart rate and blood pressure. Decreased sweating. Sepsis in severe bacterial infection.

Page 46: Acute and chronic inflammation

Thank you