SEARCH RESULTS FOR: Angioedema-Bradykinin-Mediated

Angioedema Bradykinin Mediated

Angioedema – Bradykinin Mediated: Pathogenesis and clinical findings Drug Induced Angiotensin converting enzyme inhibitor, dipeptidyl peptidase-4 inhibitor, or neprilysin inhibitor use Hereditary Type II Acquired Thrombolytic use Activate factor XII Factor XII initiates bradykinin synthesis Type I Type III Gain of function gene mutation in bradykinin cascade activators (factor XII) & precursors (kininogen), triggered by ↑ systemic estrogen Rheumatologic disorders & B- cell lymphoproliferative disease Complement cascade activation results in ↑ C1 protease production C1 esterase inhibitor is utilized to neutralize C1 protease, with its consumption exceeding its synthesis Plasma cell proliferation (i.e., dyscrasia/ monoclonal gammopathy) Immunoglobulin G antibodies act against C1 esterase inhibitor to render it non-functional Genetic or spontaneous mutation in C1 esterase inhibitor gene C1 esterase inhibitor deficiency C1 esterase inhibitor dysfunction Inhibition of angiotensin converting enzyme, dipeptidyl peptidase-4, or neprilysin induced metabolism of bradykinin ↓ Bradykinin (peptide hormone) degradation in plasma Misfunctioning C1 esterase inhibiter is unable to inactivate bradykinin cascade members ↓ C1 esterase inhibiter results in inadequate inactivation of bradykinin cascade members ↑ Bradykinin protein production in plasma Cutaneous Tissue Mucosal Tissue Epidermal layer Dermal-Epidermal Junction Dermal layer Subcutaneous layer Systemic bradykinin excess Bradykinin-2 receptor binding on endothelial and vascular smooth muscle cells Hyperpermeability pathway activation, with the transcription of some signalling molecules taking hours Released pro-inflammatory mediators act on venules & arterioles in subcutaneous & submucosa tissues Relaxation of vascular smooth muscle Dissociation of endothelial cell junctions ↑ Capillary blood flow ↑ Vascular permeability ↑ Plasma release into interstitial tissues (specific regions of the body hypothesized to be affected due to local differences in endothelial structure and its response to permeability inducing stimuli) Dilation & ↑ permeability of vasculature results in fluid release into surrounding tissues Mucosal Layer Muscularis mucosae Submucosal layer Muscularis externa Intestinal edema (Fluid buildup in Intestine tissues) Intestinal swelling (↑ intra-abdominal pressure) Laryngeal edema (Fluid buildup in larynx) Swelling in larynx ↓ air flow into & out of lungs Asphyxia (body is deprived of oxygen) Dyspnea (difficult in breathing) Author: Aaron Varga Reviewers: Tracey Rice Sunawer Aujla Shahab Marzoughi Maharshi Gandhi Jori Hardin* Yan Yu* * MD at time of publication Peripheral edema (Fluid buildup in extremities such as the hands, ankles, and feet) Ascites, bowel obstruction, &/or hypovolemic shock Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Mar 21, 2024 on www.thecalgaryguide.com