**Core Concept**
Sodium polystyrene sulfonate (SPS) is a calcium polystyrene sulfonate that exchanges sodium for calcium in the gastrointestinal tract. It is used to treat hyperkalemia by removing potassium from the body. However, its use is associated with serious side effects, including intestinal necrosis.

**Why the Correct Answer is Right**
The most serious side effect of SPS is intestinal necrosis, which is a rare but life-threatening condition. This occurs due to the formation of an insoluble complex of polystyrene sulfonate with calcium, which can cause damage to the intestinal mucosa and lead to necrosis. The use of SPS has been linked to an increased risk of intestinal perforation and peritonitis.

**Why Each Wrong Option is Incorrect**
**Option A:** Gastrointestinal bleeding is a possible side effect of SPS, but it is not the most serious side effect. While bleeding can occur, it is usually not as severe as intestinal necrosis.

**Option B:** Constipation is a common side effect of SPS, but it is not the most serious side effect. Constipation can be uncomfortable, but it does not pose the same level of risk as intestinal necrosis.

**Option C:** Hypokalemia is not a side effect of SPS, as it is used to treat hyperkalemia. In fact, SPS can cause hypokalemia as a result of potassium loss.

**Clinical Pearl / High-Yield Fact**
SPS should be used with caution in patients with a history of gastrointestinal disease, as it can exacerbate underlying conditions. It is also essential to monitor patients for signs of intestinal necrosis, such as abdominal pain, vomiting, and bloody stools.

**Correct Answer:** C. Hypokalemia