The sense of orientation is first getting confused due to the zero gravity, because the gravitational orientation is omitted.
In the vestibular organ there are sense villi with small stones lying on them which apply a pressure on the villi and by this define the direction of gravity or other linear accelerations.
But in zero-g those stones (also called otholithes) weigh nothing and so they can't apply any pressure. So there is no more up and down. The collection of rotating motion nevertheless still functions, because this works independent from gravity.
This is causing an orientation confusion and often the so-called space sickness, which comes together with nausea, sweating and vomiting. However the body quickly adapts, and at the latest after 3 days this symptoms disappear, and one feels at home in zero-g.
Then humans only orient themselves visually when moving around, and because the vestibular system doesn't supply any more useful information, it is ignored.
This picture shows different neutral (relaxed) body postures in weightlessness
In weightlessness there is no up and down, as the expedition 3 crew on the ISS here impressively proves.
In the picture above the different effects of the stay in space are again clarified on the body.
Here the differences that were observed between women and men are depicted.
Skeleton and muscles
Zero-g actually is very comfortable for the human body. Movement is done completely effortless through pushing off on solid surfaces. The body can relax completely.
The bones don't have to carry weight any more and the muscles don't have to work against the pull of gravity, that's why they atrophy. That doesn't play a big role during short stays in zero-g, but during long-term stays a significant muscle and bone loss can be measured.
That's why the astronauts have to do exercises, e. g. on a threadmill. Actually the process is an adaptation reaction of the body to the new environment, but it can cause problems at the return to Earth, when the body again has to function under earth gravity conditions.
In addition the body posture changes in zero gravity, the arms then float in front of the body, slightly bent, the upper torso is slightly curved and the legs are also slightly bent, through this the astronaut also looks smaller than he really is, like shown on the graphic. The graphic is taken from here: Evaluation of Neutral Body Posture on
Shuttle Mission STS-57 (SPACEHAB-1). To obtain another posture costs effort.
During sleep this is also the natural body posture in zero-g, which is experienced as very relaxing, according to statements of some astronauts. This is the most relaxed posture the human body can obtain.
You can try it out for yourself, underwater the body gets into the same position (This is not real weightlessness, but floating in water is very similar to zero-g. That's why the astronauts train their spacewalks underwater.)
The spine stretches itself in space by several centimeters, because no gravity is squeezing the spinal disks together. This is very often leading to backache at the beginning of a stay in space.
By the way, this is why you are taller in the morning than in the evening, because at night when you lay down, your spinal disks don't bear any load from your body weight. You can measure that!