U01.04.011 Inflammation

The inflammation response is a critical physiological process aimed at eliminating the initial cause of cell injury, removing necrotic cells resulting from the original insult, and initiating tissue repair. It is divided into acute and chronic phases. While essential for healing, the inflammatory response can be harmful if the reaction is excessive (e.g., septic shock), prolonged (e.g., persistent infections such as tuberculosis), or inappropriate (e.g., autoimmune diseases such as systemic lupus erythematosus).

Cardinal Signs of Inflammation

The cardinal signs of inflammation include redness, warmth, swelling, pain, and loss of function. These are caused by specific mechanisms and mediated by various substances.

Sign	Mechanism	Mediators
Rubor (Redness), Calor (Warmth)	The signs above impair function (e.g., inability to make a fist with cellulitis).	Histamine, prostaglandins, bradykinin, nitric oxide (NO)
Tumor (Swelling)	Endothelial contraction or disruption from tissue damage increases vascular permeability, leading to leakage of protein-rich fluid (exudate) into the interstitial space, raising interstitial oncotic pressure.	Leukotrienes (C4, D4, E4), histamine, serotonin
Dolor (Pain)	Sensitization of sensory nerve endings.	Bradykinin, prostaglandin E2 (PGE2), histamine
Functio Laesa (Loss of Function)	The aforementioned signs impair function (e.g., inability to make a fist with cellulitis).

Cardinal Signs of Inflammation

Systemic Manifestations of Acute-Phase Reaction

Systemic manifestations of inflammation can include fever, leukocytosis, and the elevation of plasma acute-phase proteins.

Fever: Pyrogens (e.g., LPS) induce macrophages to release IL-1 and TNF, which increase COX activity in the perivascular cells of the hypothalamus, resulting in increased PGE2 and a raised temperature set point.
Leukocytosis: An elevation of the white blood cell count, with the predominant cell type depending on the inciting agent or injury (e.g., neutrophils in bacterial infections).
Plasma Acute-Phase Proteins: Factors whose serum concentrations change significantly in response to inflammation. These proteins are produced by the liver during both acute and chronic inflammatory states, with IL-6 notably inducing their production.

Points to Remember

The inflammatory response is crucial for eliminating pathogens and initiating repair, but can be harmful if dysregulated.
Acute inflammation is characterized by rapid onset and short duration, often leading to the clearance of the pathogen.
Chronic inflammation involves prolonged inflammation, which can lead to tissue destruction and is associated with various chronic diseases.
Understanding the mediators and mechanisms of inflammation is key for developing targeted therapies to manage excessive or inappropriate inflammatory responses.

USMLE Step 1 Review Series

Curriculum

U01.04.011 Inflammation

Cardinal Signs of Inflammation

Systemic Manifestations of Acute-Phase Reaction

Points to Remember

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