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The respiratory system is most directly affected by changes in blood pH due to its role in regulating carbon dioxide (CO2) levels, which in turn influences the bicarbonate buffer system that maintains acid-base balance in the body. When blood pH decreases (becomes more acidic), chemoreceptors in the medulla oblongata and the carotid bodies stimulate an increase in respiratory rate and depth. This response allows for more CO2 to be exhaled, helping to raise the pH back toward normal levels. Conversely, if blood pH increases (becomes more alkaline), the respiratory rate may decrease to retain CO2, thereby lowering pH.

The endocrine system does play a role in regulating various metabolic processes and can respond to changes in pH over a longer timescale, but it is the respiratory system that provides the immediate and rapid response to acute changes in blood pH. While the immune system and circulatory system are crucial for overall homeostasis and can be influenced by pH fluctuations, they do not have the same direct and immediate regulatory function in response to changes in blood acidity as the respiratory system does.