Since there is a hollow space at the apex that can vary in size depending on apical diameter and amount of unfilled canal, and this fills with tissue fluid, microbes can grow in the fluid and pour their toxins into the periapical tissues, creating a chronic infection.
When these problems occur they occur well after treatment i.e. after restorations have been placed.
And if they go from chronic to acute, retreatment must be immediate and are frequently difficult due to the longstanding infection and restorations that have been placed.