>>If you don't want them to ask you ever again:
>> "I was just headed to the crapper to take a huge dump, my rectum is about to burst and I've already got one poking out... Would you happen to have an extra pair of pants on you?"
Actually, that would kind of make me want to ask them again. Or at least the next time I ask them I'd be saying, "How's your rectum going?" instead of "What's up?".
I think the foolhardy way to stop people asking you "What's up?" and all things nice to you, is to respond with; "Not much. Do you have five bucks I could borrow?"
I even guarantee no eye contact next time they pass you by.