Well, I didn't want to go into all the ways Frodo was debilitated during the journey, but most evident ones:

• the Morgul-blade splinter in his shoulder that never healed, as you mentioned;
• Shelob’s sting - the extent of the physical and psycological consequences of that ordeal couldn't have been light and some possibly permanent;
• Physical deprivation, from the long months of marching, poor sleep, starvation, dehydration, and exhaustion;
• Psychological/"spiritual" trauma from the One Ring trying to erode his will, the strain of fighting against Sauron's desire to dominate that is within the ring

That luxury trip package to the Undying Lands didn't come cheap.