It had to do with the expansion of slavery and the balance of power between slave and free states in the Federal government. Missouri was about to be admitted to the Union as a free state because of Northern anti-slavery politicians, and Southerners were furious. To Southern minds, if the free states in the North gained enough power, they would force emancipation on the South. Or, even if emancipation was avoided, slavery would be contained, unable to spread, and collapse on itself in violent revolt. There's a term you'll see in antebellum primary sources called 'servile insurrection.' What they're talking about is a race war along the lines of the Haitian Revolution (I know that's not exactly how the Haitian Revolution happened, but that was how Southern whites perceived it.) Southern whites feared that possibility more than anything else. As Edward Baptist writes in The Half Has Never Been Told,

"Over the previous decade, Congress had been admitting states in pairs, retaining a rough balance between North and South in the Senate. Southern senators turned back the House’s bill and struck the antislavery clauses. In response, the House rejected the Senate’s version of the Missouri statehood bill. And as speeches grew more heated, John Quincy Adams realized that they “disclosed a secret,” a subterranean fault line—the fact that almost all northern representatives would, if pushed to the test, vote against more slavery expansion. Meanwhile, southern representatives were deciding that the right to expand slavery was inseparable from any other right that they possessed. John Scott, the nonvoting delegate from Missouri, insisted that restriction would deny Missouri whites their constitutional right to property. The right to expand was even the right of self-preservation. If slavery restriction blocked further expansion, southern representatives wailed, slave numbers would balloon until a black rebellion erupted, making a giant Haiti of the southern states. Thomas Cobb of Georgia warned that the friction of slavery restriction was “kindling a fire which all the waters of the ocean could not extinguish. It could only be extinguished in blood!” (Baptist, The Half Has Never Been Told, pp. 154-155)

So if you're ever wondering, the fear of annihilation in a race war that never came to pass was a big reason that slaveholders were so violent in their defense of slavery. As absolutely deranged and sickening as it is, to them the defense of slavery and the defense of their families were one and the same. When they talked about defending their homes and families by killing and dying for slavery, they actually believed it. Southerners considered slavery to be the foundation of their society, its potential dissolution to be equivalent to an apocalypse, and were therefore willing to deploy any and all means in it's defense.