Tears are very complex fluids. Their job is to lubricate, moisturize, and oxygenate the corneas and inner eyelids, to be antibiotic/antiviral, to break down byproducts, etc. They're continually produced and their composition changes with environmental demands (e.g., they're more acidic at the end of the night, there are more of some types of enzymes).
When your eyes are tired, you blink less, and so you bathe your eyes much less frequently in natural tears. Thus your eyelids and corneas have more of the chemicals in tears that weren't washed away and replaced.
What about artificial tears? Or plain water?
- not continually replenished
- likely your eyes aren't moisturized/oxygenated/lubricated nearly as well
- because even artificial tears are very different chemically
If you want to learn more, here's a pretty readable chapter looking at what happens in a similar "adverse" situation -- while wearing contact lenses:
Environmental Conditions and Tear Chemistry
National Research Council (US) Working Group on Contact Lens Use Under Adverse Conditions; Ebert Flattau P, editor.
Washington (DC): National Academies Press (US); 1991.