An American colleague of mine used to greet me every morning with question 'what's up?'. I would reply 'Nothing' or 'I'm fine.'
After the third time it occurred to me that for her the question was an all purpose greeting, as in the film title What's Up, Doc
To these British ears it meant 'what is the problem?' or 'is something wrong?'. This confusion is receding, for better or worse. Most younger native speakers now recognise both usages