Kallikrein-kinin system

Kallikrein-Kinin System

The Kallikrein-Kinin System (KKS) is a complex enzyme cascade that plays a critical role in blood pressure regulation, inflammation, pain, and blood coagulation. It is part of the broader plasma protease systems, which include the coagulation system, fibrinolytic system, and the complement system. The KKS is primarily involved in the production of kinins, potent vasodilators that are involved in processes such as blood vessel dilation, permeability, and the mediation of inflammation and pain.

Components

The KKS consists of several key components:

• Prekallikrein (PK) - A plasma protein that is converted into kallikrein by the action of Factor XII (Hageman factor).
• Kallikrein - An enzyme that cleaves kininogen to release kinins, mainly bradykinin.
• High-Molecular-Weight Kininogen (HMWK) - A substrate that is cleaved by kallikrein to release bradykinin.
• Bradykinin - A peptide that induces vasodilation, increases vascular permeability, and is involved in the mediation of pain and inflammation.
• B2 receptor and B1 receptor - Receptors that bind bradykinin and mediate its effects.

Function

The primary function of the KKS is to regulate blood pressure, inflammation, and pain through the production of kinins. When tissue injury or inflammation occurs, the KKS is activated, leading to the cleavage of kininogen by kallikrein, which results in the release of bradykinin. Bradykinin then binds to its receptors on endothelial cells and other cell types, triggering a series of responses that include vasodilation, increased vascular permeability, and the sensation of pain. These responses help to facilitate the movement of immune cells to the site of injury or infection and promote the healing process.

Regulation

The activity of the KKS is tightly regulated by various mechanisms to prevent excessive inflammation and blood pressure changes. One of the main regulatory mechanisms is the action of kininase II, also known as angiotensin-converting enzyme (ACE), which degrades bradykinin into inactive peptides. Additionally, the levels of kallikrein and kininogen are controlled by various hormones and cytokines that modulate the system's activity in response to physiological needs.

Clinical Significance

Dysregulation of the KKS can lead to various pathological conditions. Overactivity of the system can contribute to edema, hypotension, and inflammatory disorders, while underactivity can result in impaired blood pressure regulation and reduced protection against infections. The KKS is also a target for therapeutic intervention in conditions such as hypertension, heart failure, and hereditary angioedema. Drugs that inhibit ACE, thereby increasing bradykinin levels, are commonly used to treat hypertension and heart failure.

See Also

• Coagulation system
• Fibrinolytic system
• Complement system
• Angiotensin-converting enzyme