An expression of great misfortune, expanded from it's original meaning, to be pregnant. The expansion is due to the expression often being the unfortunate case of the pregnancy being untimely and unpredicted.
"When they find all the coke in Mark's desk, he's gonna be sooooo up the duff!"
"Shit, I've got 2 flats and only 5 minutes to get the airport!"
"You are up the duff mate"