Which of the following conditions is associated with an increase in ionized calcium (Cai) in the blood?

Ionized calcium (Cai) refers to the portion of calcium in the blood that is not bound to proteins and is biologically active. The condition that is associated with an increase in ionized calcium is malignancy, particularly due to certain types of cancers that can lead to hypercalcemia. This can occur through various mechanisms, such as the production of parathyroid hormone-related peptide (PTHrP) by malignant cells, which mimics the action of parathyroid hormone and causes the bones to release calcium into the bloodstream.

In contrast, alkalosis can lead to a decrease in ionized calcium due to increased protein binding of calcium, particularly to albumin. Hypoparathyroidism typically results in low levels of calcium in the blood, as parathyroid hormone is responsible for raising calcium levels. Hyperalbuminemia might also lead to falsely increased total calcium levels but does not account for an increase in ionized calcium since it is the unbound fraction that is biologically active.

Thus, malignancy can directly increase the levels of ionized calcium in the blood, making it the correct answer in this context.