Charlie had a very hard life in the last 4 years. He lost his parents and had to raise his 4 siblings since then. Initially he wasn't good at it, he was immature yet, but little by little he grew up, he became a real father for them and even met the love of his life. They didn't get married, but she was like his wife and they somehow raised "their kids" (Claudia and Owen), and runned the house, having Bailey and Julia's support and help. In sickness and in sorrow, he took care of her like no one else could, willing to do anything to heal her, and share their whole life together. But then he lost her, for the most tragic reasons besides death, he just lost her. Time passed and he thought he could start over. He thought "life goes on", and recently he met Nina, a nice woman who's great with him, Owen and Claudia. But life is not so simple, persons can't easily move on, forget or avoid the past suffering like nothing happened.
In this episode, Charlie seems to be happy with Nina, and they talk in the restaurant about how she visited Salinger's as a child, that maybe she already met him before. Later, in dinner with the family, he's rude to Griffin for eating too much food (and for the mistake he did with Julia), and also plans the restaurant reopening. Claudia asks if he'd hire Reed but he says all the jobs are covered, so Griffin hires him in the bike shop. After dinner, Griffin tells Julia that her brother hates him and she thinks different, that they have a lot in common so they should get along well. Charlie tells Nina why he doesn't like Griffin, that he and Julia together are a disaster waiting to happen. She tries to light up this saying that he has to accept it, and kisses him. And right then, happens one of the key moments of the series: 10 months after Desperate Measures, Charlie sees the love of his life back in SF, leaving the Roosevelt hotel. He's totally shocked and stunned, feeling how much he'd have loved to see her again, touch her face, hold her hand. How much he'd love to be waking up next to her every day of his life if things would have been different. He sees her leave in a cab, and Nina asks him what happened since his face is pale and shocked. At home, he confides in Claudia about what this means, he thinks he's hallucinating, that he might not be ready to move on. She notes that he's really distracted and out of his mind because while talking he puts the clean and dirty dishes anywhere instead of where they belong. The next morning he finally encounters Kirsten near the house, she's healthy and moving back. He is very happy to see her and pretended her to call him while returning to SF, but she can't answer as they are interrupted by a broker (this proves that he really wanted to see her again). They agree to have a dinner later in the night at the hotel. Then, at Salinger's, Nina notes that he talked about Kirsten as the love of his life, his great true love so she is worried, but allows him to have dinner with her to have a "closure". But that night, Charlie receives one of the worst news of his life: Kirsten got married 2 months ago to another man, Paul, a doctor from Chicago. She says she was reluctant to tell him because she didn't know what it meant, obviously aware that this could hurt him. His first reaction is the natural and the true one, he's stunned, devastated and can't even answer (he was even sweating and wanted to loosen his tie). After a while he says he is seeing someone (Nina) but it's obvious he's not fine. To cause him even more pain, the stupid of Julia coldly tells him to move on and get over it because marriage is it (Julia might think that because she feels superior, but the future will prove she has no idea what she's talking about). And to make things even worse, Griffin mistreats him badly for being miserable and not accepting the happiness of the rest. Then, Charlie "builds a wall" hiding his true feelings: he visits Kirsten at the hotel, recognizes that last night was horrible and pretends to be happy for her, telling her that he only wanted her to be happy, even if it's not with him. He says the kids will want to see her, they hug and he tells "I love you Kirsten", and she says "I love you too", proving that their deep love for each other remains there, intact (and knowing the truth, the scene becomes really tearful). Then, he also pretends for Julia and Griffin, offering a wedding, and also lies to Nina faking happiness. This story is great because everything is a lie, the truth is that Charlie is broken, deeply devastated and sad. After all the things he did for Kirsten in early season 3, he can't deal with this now without being hurt. Bailey deals with the pain with alcohol and partying (this was showed when Jill died and in season 3), but Charlie deals with the pain inside, he doesn't express his suffering, like he did in the episodes Thanksgiving, Personal Demons, Christmas, The Wedding, Spring Breaks, etc. And this have big consequences on his body. I know this for personal experience, major traumas happens, the big stressful situations of life, and some people pretend they are ok but all the pain and the suffering comes out in an illness. The body suffers. After the episode Zap, Charlie recovered from his first symptoms but it's very likely Kirsten's news that broke his heart one more time after Desperate Measures, and Julia and Griffin's bad attitude and selfishness towards him, provoked the final growth of his tumor, causing his collapse in the next episode.
On the other hand, Bailey-Annie story is not great but being together makes good to both of them, despite John's advice against it (Bailey's sponsor from AA). The problem is that hurts Sarah. In season 3 finale she thought this would be easier but now she realizes it's painful. Claudia is disappointed of her crush on Reed, and though Julia tries to help her, it seems harder than it looks. Anyway, Claudia's part disappointed me here. There was no scene showing her reaction to Kirsten's news. Considering her slip up in 3x05, she is partially and indirectly guilty of what happened, so she should have said something to Charlie or show some reaction towards Kirsten for marrying someone else (Claudia reacted in 2x09, 2x13, 3x06). Leaving that aside, I praise the writers job here, Kirsten had to return, I preferred her to be single yet, but her marriage is one more reason for Charlie's illness to be more painful. Now, guessing the off screen story, considering her words today, the heartbreaking final moments of Desperate Measures in early December of 1996, and her chronic mental illness: she spent a very sad Christmas suffering for losing Charlie and his family definitely. Probably she cried more when she received back her stuff he sent her in 3x13, watching their happy pictures, Claudia's, etc. But with her parents and her sister's company, and the medication, little by little she started to recover herself. After Christmas and New Year's Eve, she surely ran into Paul and told him all the story, and he tried to understand and comfort her. Months passed, Gene and Ellie were relieved to see their daughter getting better and finding comfort and peace with a neuropediatric surgeon who knew her since highschool. The two fell in love, that common love you can find in life, sustained by their common interest like child neurology-psychology or Chicago, yet cannot be compared to Charlie's love, infinitely more stronger, true and special. Gene and Ellie approved and pushed Kirsten's marriage with Paul for two reasons: first, to let her live her own life so they don't have to take care of her forever, and second, to get rid of Charlie forever, make her forget about him. Kirsten happily agreed with the first reason since her parents drove her crazy sometimes, besides she said in 3x12 that she didn't want to be told what to wear and what to eat everyday. But she found much harder the second one, she hated to let the love of her life go, but they (including the therapist) convinced her it was for the best, so she and Paul started to think that too. But here Kirsten's illness played a big role. Everyone around thought that this was a good idea surely because Kirsten, having BD II as chronic illness, would be safe and happy with a neuropediatric surgeon. She recognized today that the engagement with Michael was a weird/bad choice (see how much she talked in psychotheraphy), and now she thinks this is a good thing, supported by her family. Anyway, one day, she moved out her parents house to live with Paul and then, in late august, they got married in a simple very small ceremony, just family present, to avoid any risk of a relapse in Kirsten (a bigger event could have re triggered the bad memories and so, a hypomanic episode). Then, with Gene finally sure, he allowed Kirsten's idea to return to SF, and I guess she pleaded Paul to take a job here, because despite that he had all his life, family and friends made in Chicago, she hadn't. She missed all, like she said in Desperate Measures. In that moment she said "there's nothing here", and 10 months later that didn't change much. Probably he had doubts, but he accepted to make her happy. And that's why she's back on town. Sadly, she couldn't return alone and single, wanting to get back with her lost husband because her parents, therapist would have never allowed that, and convinced her that she couldn't. So here, what Charlie said exactly one season ago to Ellie was accomplished: she and Gene sold out their daughter. They took their daughter away from her true home and gave her to a doctor, feeling she would be safe and happy. And though seemingly things are fine for her, the future will show that deep down she built her own wall to avoid the suffering, to cover that deep wound caused for losing the man she always loved.
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