Gentlemen, remember Hollywood still has to make an entertaining story.
That being said...
Issue #1
Hygiene
Leaving the civilized part of the world, humans venturing out west were not able to bathe on a daily basis and wash their clothing on a regular level. many people wore the same set of clothes for weeks while sweating and accumulating dirt and grime. bacteria caused rampant skin infections and orifice infections.
Women had to use whiskey and any animal product soap(harmful) to wash hair and their lady parts. Feminine hygiene products were not available like today. Monthly "Curse" was used with a small rag inserted like a plug. They didn't shave armpit or leg hair on the trail. They had it worse.
Dental decay was rampant due to lack of dental preventive products. Teeth removal happened usually after a bottle of whisky and a powerful yank from anything able to latch onto the tooth.
Toilet paper? Use what was laying around.
Issue #2
Food
Beans. Nightly game of pointing fingers.
Game. Huunt. Kill. Skin. Gut. Cook.
Water. Piss poor. They didn't know about boiling.
Issue #3
Ammo
Scarce as you use it from the beginning to end. Outposts may had some. Pillage what you could find.
Issue #4
Weather
Thunderstorms, wildfires and snowstorms. Get caught and you ould die.
Issue #5
Those trying to take everything from you.
Thieves, bandits, militias, indians, and cowboys.
I like the show. Sam Elliot is the best when he looks at you in his gravely voice and says "I'll kill you."
I salute all those brave pioneers who made those treks across the untamed territiries.