Cause of Itachi's Death.
Chakra is a form of energy all living individuals naturally produce to some degree. It exists within every cell of the body and is composed of the mixing of two energies: physical, which is energy collected from the body's cells and spiritual, which is collected from the mind's consciousness. Notably, physical energy is the application of vitality or Yang, whereas, spiritual energy is the application of administration of imagination or Yin. Different ratios of these two energies create different formations of chakra. The more powerful these two are the more powerful jutsu a person is able to use.
This energy or chakra channels through the chakra circulatory system— which is the equivalent to the circulatory systems network of blood — to any of the 361 pressure points, that reside in the body. Signifying, that the chakra pathway system is entangled into the body and like blood vessels it touches and interacts with every single living cell and passes through every organ. 
- A mythic individual known as, the Sage of the Six Paths, discovered and preach about the mysterious of chakra.
Rikudō Sennin was an individual that possessed a Dōjutsu: Rinnegan — who discovered the truth of chakra, and founded the arts of Ninjutsu creating the shinobi world. He possessed an ethereal quantity of both physical and spiritual energies, which caused him to create a technique amongst his own arts: Banbutsu Sōzō — an ability that is the application of administration of imagination, and the spiritual energy or Yin to create physical forms from nothingness. Then, through the application of vitality, and the physical energy or Yang, he breathes life into those forms, resulting in creations. 
His energy would be divided among his children: his Elder Son, and his Younger Son. The Elder Son would inherit a form of his father’s Dōjutsu, as well as his powerful chakra and spiritual energy. His descendants would become the Uchiha — a clan that is famous for their powerful chakra, exceptionally strong techniques, and prodigious aptitude for combat. The clan also possesses a Dōjutsu: *Sharingan, a Kekkei Genkai which gives them the ability to see the "colours" of chakra, allowing them to analyze and copy their opponent's skills, along with a number of other abilities — this Kekkei Genkai evolves into higher state, known as the Mangekyō Sharingan. 
Reflectively recall, that the Uchiha, through inheritance, possess an overwhelming quantity of spiritual energy. Unlike the Younger Brother’s descendants, the Senju, the Uchiha lack the necessary physical energy to sustain their spiritual abilities for extended periods of time (Amaterasu, Tsukuyomi), and regarding these abilities, Susano’o is the most harmful to the users of the Mangekyō. 
Susano’o is the third ability granted by the Mangekyō Sharingan to those who awaken the abilities Tsukuyomi — which symbolizes the "darkness of the spiritual world" and Amaterasu — which denotes the "light of the material world" it manifest as an ethereal being surrounding the user of the Mangekyō, simultaneously, consuming the user’s life.  The Mangekyō techniques, Amaterasu, and Tsukuyomi, both require a different ratio of physical and spiritual energy, in order to be use. However, Susano'o requires the same ratio.
Susano’o affects the user differently from the other precondition Mangekyō techniques — which only strain the user’s eyes and body, whereas Susano’o consumes the user’s life.
As mentioned earlier, the Uchiha have an unequaled distribution of spiritual energy as opposed to physical energy or Yin and Yang, which they inherited from their ancestor. As a result, the Uchiha require energy of high vitality to balance and prolong the use of their eyes.  These energies travel through a network of complexities that entangle chakra and blood that determine the vitality of the cells. Essentially meaning, that the physical energy or Yang existing in the Mangekyō Sharingan loses its vitality; thus it’s left with pure spiritual energy or blindness, however, when met with its opposite: high concentrations of physical energy or Yang (Hashirama Senju) material, the vitality of an Uchiha’s Mangekyō Sharingan is evenly matched, allowing them to use it much longer than a standard Mangekyō Sharingan. Additional, this physical energy can be restored through a tighter the blood ties are between the "donor" and the "receiver" of the Mangekyō Sharingan.  
Susano’o is a severely heighten from of the tension on the user’s body. Because of the Uchiha’s inheritance of Yin, Susano’o existence cannot be used for extended amounts of time like the preceding abilities before it. Principally because Susano’o is a highly dense chakra construction. What is chakra composed of physical energy and spiritual energy. Unlike Tsukuyomi or Amaterasu, Susano’o requires a high-amount or ratios of Yang to keep it constructed. Where does it get it? The body, specifically the physical energy residing in the cells of the body. 
Susano’o destroys the cells of the human body to stay manifested. By destroying these cells, the chakra pathway system connections cannot function correctly, and destroys the cells within every organ in the body. 
And it is probably where Itachi Uchiha contradicted his illness — resulting in Pulmonary embolism...?  
Susano'o may have been the prime factor that strained the illness acquired by Itachi, and saw throughout the story. Shit crazy...