While largely a clinical diagnosis, the definitive diagnosis can be made with measurement of compartmental pressures. Pain with passive stretch is widely considered the most sensitive exam finding, while paralysis and pulselessness are late findings that are often irreversible. The physical exam findings in compartment syndrome are often referred to as the “5 P’s”: pain with passive stretch of the toes/ankle, paresthesias, paralysis, palpable swelling, and pulselessness. Recognition of compartment syndrome is essential for the treatment and prevention of ischemia and necrosis of the neurovascular structures and muscle. Fractures are the most common cause of anterior compartment syndrome, accounting for over 65% of the cases. The most common causes of anterior compartment syndrome are trauma (fractures, crush injuries, contusions, gunshot wounds), tight casts or dressings, extravasation of IV infusion, burns, post-ischemic swelling, bleeding disorders, and arterial injury. When the pressure inside the anterior compartment increases, tissue perfusion can be compromised, which may lead to irreversible muscle and nerve damage – muscle necrosis. The anterior compartment of the lower leg is the most common site for acute compartment syndrome. Errors in Hox gene expression can lead to malformations in the limbs. These genes control patterning and consequently morphology of the developing limb in the human embryo. SHH activates specific HOX genes – Hoxd-9, Hoxd-10, Hoxd-11, Hoxd-12, Hoxd-13 – which are essential in limb polarization and regional specification. The zone of polarizing activity (ZPA) produces SHH, promoting the organization of the limb bud along the anterior-posterior axis. The specific fibroblast growth factor involved in hindlimb development is Fgf10, which is stimulated by Tbx4. The apical ectodermal ridge (AER) produces a fibroblast growth factor (Fgf), which promotes the outgrowth of the limb buds by stimulating mitosis. Retinoic acid is a global organizing gradient that initiates the production of transcription factors that specify regional differentiation and limb polarization.

Several factors influence the formation of the limb bud vasculature and musculature including retinoic acid, sonic hedgehog (SHH), HOX genes, apical ectodermal ridge (AER) and the zone of polarizing activity (ZPA). The limb buds of the embryo begin to form about 5 weeks after fertilization as the lateral plate mesoderm migrates into the limb bud region and condenses along the central axis to eventually form the vasculature and skeletal components of the lower limb.

4 compartments of leg