Microgravity affects just about everything in the human body, and usually for the worst. Fortunately, the effects are seldom more than temporarily disabling: humans are very good at adapting. And when astronauts return to Earth, they normally re-adapt very quickly to the customary, gravity-bound environment.
The vestibulary system and "Space Adaptation Syndrome"
We take our ability to stand upright just as much for granted as we do the force of gravity that holds us to the Earth. In fact, the human sense of balance depends on an extremely sophisticated sensor system that provides a constant stream of information to the brain. The key motion sensors are the subtle organs of the vestibulary system inside the inner ear. These function as super-sensitive accelerometers feeding the brain with a steady stream of signals that indicate motion and direction. There are also pressure receptors in the skin and in muscles and joints. Our senses of sight and hearing complete the data stream. Without having to think about it, we usually know everything we need about our body's posture and state of balance.
In the absence of gravity, signals from the vestibulary system and the pressure receptors are wildly misleading. The effect usually leads to immediate disorientation: many astronauts suddenly feel themselves upside-down, for example, or even have difficulty in sensing the location of their own arms and legs.
This disorientation is the main cause of the so-called Space Adaptation Syndrome, which one astronaut wryly described as "a fancy term for throwing up". Half or more of all space travellers suffer from space sickness, which brings with it headaches and poor concentration as well as nausea and vomiting. Usually, though, the problems disappear within a few days as astronauts adapt.
It is their brains, not their stomachs, that do most of the adapting. The confusing signals from the inner ear are largely ignored and vision becomes the prime source of "balance" information. In space, "down" is where your feet happen to be.