INFLAMMATION – L3

SEQUELAE OF AI Depends on the type of tissue involved and the amount of tissue

destruction, both of which depend on the nature of the injurious agent (pathogen / chemicals etc…).

4 Possible outcomes:• Resolution• Suppuration• Organisation• Chronic Inflammation (CI)

RESOLUTION• Complete restoration of the tissues to normal after an episode of

acute inflammation.• The conditions favouring resolution are:• Minimal cell death and tissue damage• Good regenerative capacity of tissues like the liver

• Rapid destruction of the causal agent (by phagocytosis)• Rapid removal of fluid and debris (by good vascular drainage)

E.g.: Acute Lobar Pneumonia• The alveoli are filled with the AI exudate containing fibrin, bacteria

and polymorphs. The alveolar walls are thin and have many capillaries (for gas exchange) and lymphatic channels.

• Sequence of events leading to resolution:– Phagocytosis of pneumococci by neutrophils– Fibrinolysis– Phagocytosis of debris (mainly by macrophages)– Carriage of debris through lymphatic system to the lymph nodes– Disappearance of vascular dilatation

• Following this, the lung parenchyma appears histologically normal

SUPPURATION Formation of pus (a mixture of living, dying and dead neutrophils;

bacterial and cellular debris; sometimes globules of lipid). Conditions which favour suppuration are:

• Persistence of causative agent• Virulence of causative agent

ABSCESS: Once pus begins to accumulate in a tissue, it is surrounded by a pyogenic membrane consisting of sprouting capillaries, neutrophils and occasional fibroblasts. Bacteria within the abscess are inaccessible to antibodies and antibiotic drugs (e.g., it is very difficult to treat acute osteomyelitis which is an abscess in the bone marrow cavity)

ORGANIZATION Replacement of damaged tissue by granulation tissue. Circumstances leading to organization:

• Large amounts of fibrin are formed, which cannot be removed by fibrinolytic enzymes

• Substantial amount of tissues become necrotic or if the dead tissue is not easily digested (e.g., fibrous tissue)

• Exudate and debris cannot be removed or discharged During organization:

– New capillaries grow into the inflammatory exudate– Neutrophils and macrophages migrate into this zone– Fibroblasts proliferate, resulting in FIBROSIS

• E.g., Cirrhosis in liver following AI

CHRONIC INFLAMMATION Is the inflammation of long duration in which the tissue destruction

and repair process continues simultaneously with active inflammation.

Occurs when the agent causing AI is not removed or destroyed (AI then progresses to CI)

Features:• Fever, Leukocytosis and ↑ed ESR• Organization of the tissue• Lymphocytes , plasma cells and macrophages gradually replace the

neutrophil polymorphs in the inflammatory exudate• E.g., Granulomatous inflammation: often seen in certain infections

like TB. A granuloma consists of epitheloid macrophages and giant cells surrounded by lymphocytes.

Granulomatous TB

WOUND HEALING OR TISSUE REPAIR Tissue repair is a sequel in every case of tissue damage associated

with inflammation. The process involves:• Response to the injury in the form of active inflammation• Regeneration and proliferation of parenchymal cells and connective

tissue cells• Synthesis of Extra Cellular Matrix (ECM) proteins• Remodelling of connective tissue and parenchymal cells• Collagenisation (to increase the strength of the wound)

For Your Info …

Granulation tissue is collagen-rich tissue which forms at the site of an injury. As the body heals, this tissue fills in the injury, and may eventually scar over.

The ECM proteins play a very important role in remodelling of tissue or organ after an injury. The ECM consists of: Fibrous proteins (collagen and elastin); Adhesive glycoproteins (fibronectin and lamillin); Proteoglycans and hyaluronan;

Fibrosis in liver:

A fibroblast is the most common type of cell found in connective tissue. Fibroblasts secrete collagen proteins that are used to maintain a structural framework for many tissues. They also play an important role in healing wounds.

Virulence: The ability of an agent of infection to produce disease. The virulence of a microorganism is a measure of the severity of the disease it causes.

To be continued …