Yes, it's a pretty flexible term, *but* can be used to express concern; for example: 'What's up? Did Manchester United lose again?' ;) No *genuinely*, if someone looks distressed or worried. I never use it as a casual greeting, but I guess I'm an exception.
Oh, to answer your question, you could then answer: 'Yeah, it's time they got (yet) another manager' or 'I've got a bad headache/stomach ache through trying to learn English.' ;-)