Tsunade lost the people most important to her.
And I mean, she was already known as the medical expert and still failed to save her lover. I'm sure that makes you blame yourself at least some amount.
Didn't Orochimaru's parents die when he was a child or something? I'd say Tsunade's past is worse, since she lived a pretty good life until then, even if during wars. Then suddenly her happiness was just taken away and she was left without anything.
I honestly completely forgot about that.
And I disagree. Your parents dying at a young age is worse than losing your younger brother and lover.
I still disagree though, she was trolled by life big time. First giving her everything and then taking it away in an instant.
Orochimaru grew up coping with the fact that he lost his parents. Like Iruka for example. :|
I'd actually be sadder if my sibling died compared to my parent.