Ghirga said prosecutors leaked investigative documents that were to be kept secret, and he repeated charges that the blade of the alleged murder weapon did not match the cuts on Kercher's throat.
Besides facing murder charges, Knox is simultaneously being tried for slander since at one point she implicated Patrick Lumumba, a bar owner who she worked for at the time.
She mentioned Lumumba's name during her interrogation when she gave an odd confession, telling police that she had a vision of being at the murder scene the night Kercher was killed. She told police that Lumumba was also there.
Lumumba was later cleared of any involvement in Kercher's death and is suing Knox. Conviction of slander could result in a six year prison sentence.
Ghirga spent a considerable amount of time defending Knox against the slander charge.
Addressing the jury, he said that they have to decide whether "what Amanda said that night, her implosion, was the collapse of her alibi or evidence of utmost stress."
He cited a police offical who was in the building that night who heard Knox's screams down the hall. "How can someone give a serene statement" if she was yelling, he asked.
Ghirga said police were aggressive and critical of Knox until she signed her statements, and only later were they nice to her and took her for coffee.
Turning to Knox, Ghirga asked, "And then what happens Amanda? What do they do? Handcuff you?"
Prosecutors ended their case later in the day with a rebuttal statement, particularly attacking the defense's claim that they had presented little in the way of a motive to explain Knox's vicious attack on her roommate.
Prosecutor Giuliano Mignini called Knox a "coiled spring that was unleashed that night."
"Meredith accused Amanda of a series of things, that Meredith must have considered unbearable: she brought boys home, she had a vibrator and condoms, she didn't flush the toilet," Mignini told the court.
The two men were willing to help her because "Raffaele always followed Amanda, and Rudy also tried to please her. The three of them were full of drugs and alcohol and things degenerate quickly in those conditions."
Her confession of having a vision of being at the murder scene was not coerced and it was not improper that a lawyer wasn't present, the prosecutor said.
"I asked Amanda if she wanted to make a spontaneous statement, and she said yes. In that situation the presence of a lawyer is not necessary. If a prosecutor questions a person, then a lawyer must be present," he said.
That statement was signed at 5:45 a.m.
Lawyers for the defense will get one last chance to rebut the prosecution and the jury is expected to begin deliberations by Friday.
ABC News' Nikki Battiste contributed to this report