As for other differences between typical pistols (including the .22) and more powerful rounds like the .223 you have to understand an important fact about high powered weapons:
What kills you isn't necessarily the hole in your body or the shredding of your insides, it's that parts of your cardiovascular system explode, particularly in the brain. Basically as the round enters your body, it creates a pulse of pressure in your bloodstream, which causes hemorrhaging. You die from massive brain bleeding before the damage from the primary would kills you.
It's called hydrostatic shock.
Hunters know this very well, it's what results in "blood shot" meat near the wound that you have to avoid when harvesting the meat. Bloodshot meat is a more localized effect, but it's the same thing (hemorrhaging caused by induced static hydraulic pressure in the cardiovascular system).
A .22 doesn't produce anywhere near enough energy to cause hydrostatic shock. Typically the minimum is considered to be the energy from a .45ACP, which is about half the energy of a .223/NATO