How would one ascertain what the bottleneck is on a system with high memory (128 GB RAM) and starts getting peculiar errors when there's only 10-20 GB remaining free?

I'm getting various odd issues that are not being enumerated in the system log, but include apps not opening sometimes and no mountable file systems.

When I close a significant number of applications, the system begins to start behaving properly again, but doesn't really behave entirely right until a reboot.

I'm assuming that I do not have enough file handles available or my maxproc settings are too low, etc. What would I need to do to determine the actual limits that are causing problems?

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