Welcome to MRC Psycho Big Go. Revision is a child. My name is Calico. I missed a chin in the SSCO. Many of you spend a lot of time for YouTube. So I started this podcast to help you revise in the goal. Each episode breaks down one hailed topic, mapped to the syllabus. This is then followed by five questions to help reinforce your learning. So grab your headphones, turn travel time into revision time, and let's get started. In episode 25, we explored emotion regulation and the role of the limbic system in emotional processing. In this episode, we begin a new series on stress. We start with the foundations, what stress actually is and what it does to the body. One way to describe stress is a state of threatened homeostasis. This is the disruption of the body's internal equilibrium by external or internal demands. A stressor is any stimulus that threatens homeostasis. Stressors can be physical, such as injury or infection, or psychological, such as financial pressure, relationship breakdown or bereavement. The stress response is the body's attempt to restore balance. Remember, stress refers to a state of threatened homeostasis. A stressor is any stimulus that disrupts internal equilibrium. The scientific study of stress was transformed by the work of Hans Seelia, an Austrian Canadian endocrinologist born in Vienna in 1907. Seely trained in medicine in Prague and later moved to Montreal, where he spent most of his career. His discovery of stress began in a way that is both scientifically important and, it has to be said, a little undignified. By his own admission, Seely was a clumsy laboratory technician. As a young researcher in the nineteen thirties, he was attempting to identify a new sex hormone by injecting rats with ovarian extracts. The problem was that he kept dropping them, chasing them around the laboratory and handling them rather badly before managing to inject them. When he examined the rats, they had all developed the same triad of physical changes, enlarged adrenal glands, shrunken immune tissue, and gastric ulcers. Selly realized it was not the substance being injected that mattered. It was the nonspecific demand placed on the body by any noxious stimulus, whether chemical or simply being manhandled by a clumsy researcher. He called this nonspecific response stress and devoted the rest of his career to understanding it. He published his landmark paper in Nature in 1936 and later developed his findings into the general adaptation syndrome. Remember, Hans Selyer described the body's nonspecific response to any noxious demand, which he called stress. Sely proposed that the body responds to any stressor through a predictable three-stage process, which he called the general adaptation syndrome. Stage one is the alarm stage. This is the immediate response to a stressor. The body perceives a threat and mobilizes its resources through the sympathetic adrenal medullary system, or SAM. This triggers the classic fight or flight response within seconds. Heart rate and blood pressure increase. Adrenaline and noradrenaline are released from the adrenal medulla. Blood is diverted away from the gut and towards the muscles. Breathing quickens and pupils dilate. Celia noted that resistance to the stressor temporarily drops during the initial shock phase before recovering as the body mobilizes. Stage two is the resistance stage. If the stressor persists, the body attempts to adapt. The SAM system is fast acting, but not built for sustained demands. As the acute sympathetic response subsides, a slower, more sustained system takes over. The hypothalamic pituitary adrenal axis or HPA axis. The hypothalamus releases corticotropin releasing hormone. This stimulates the pituitary gland to release adrenocorticotropic hormone. This in turn stimulates the adrenal cortex to release cortisol. Cortisol is the primary stress hormone of the resistance stage. It mobilizes energy by raising blood glucose, suppresses immune function, and maintains cardiovascular tone. During this stage, the individual appears to cope, but physiological resources are being steadily depleted. Stage three is the exhaustion stage. If the stressor continues and the body's adaptive resources are exhausted, the individual enters the third stage. Cortisol levels remain chronically elevated, causing progressive damage to multiple organ systems. The consequences of chronic stress and HPA axis dysregulation include immunosuppression and increased susceptibility to infection, cardiovascular disease, metabolic disturbance, hippocampal atrophy, impaired memory and concentration, and an increased risk of depression and anxiety disorders. Remember, cellules general adaptation syndrome describes three stages. The alarm stage driven by the fast acting sympathetic adrenal medullary system, the resistance stage in which the slower hypothalamic pituitary adrenal axis takes over with cortisol as its primary hormone, and the exhaustion stage in which prolonged stress leads to physiological damage. A useful mnemonic to remember the three stages is ARE, A for alarm, R for resistance, E for exhaustion. But what is the clinical significance of this in psychiatric practice? Chronic HPA axis. Dysregulation is one of the most consistently replicated biological findings in major depressive disorder. Elevated cortisol and failure to suppress cortisol on the deximethasone suppression test have been documented in depression for decades. Cortisol is toxic to the CA1 pyramidal hippocampal neurons at high concentrations, and hippocampal volume reduction is seen in patients with chronic stress, PTSD, and recurrent depression. This may partly explain the cognitive difficulties, particularly memory impairment, seen in these conditions. Remember, chronic, hypothalamic, pituitary adrenal axis, dysregulation and elevated cortisol are implicated in major depression, post-traumatic stress disorder, and cognitive impairment. Cortisol-mediated hippocampal atrophy may link prolonged stress to memory difficulties and increased psychiatric vulnerability. It is also important to distinguish between acute and chronic stress as their physiological and psychological effects differ. Acute stress is short-lived and generally adaptive. The alarm response mobilizes the body efficiently, the stressor passes, and the system returns to baseline in moderate amounts. Acute stress can enhance performance and alertness. Chronic stress, by contrast, is prolonged and often insidious. It occurs when stressors persist over weeks, months or years, such as in the context of poverty, relationship conflict, workplace pressure, or caring responsibilities. Chronic stress is associated with the exhaustion stage of Celia's model and with the greatest risk of physical and psychiatric harm. Now let's test your recall. I will read out five exam style questions. After each one, I will pause for 10 seconds so you can attempt them before hearing the answer. Question one. A 45-year-old nurse presents with fatigue, recurrent infections, and low mood after caring for a critically ill relative for eight months. Using Silly's model, which stage of the general adaptation syndrome best explains her presentation? The exhaustion stage prolonged stress has depleted her adaptive resources. Question two What are the three stages of Selly's general adaptation syndrome in order? The alarm stage, the resistance stage, and the exhaustion stage. A useful mnemonic is ARE. Question three. Which hormone is the primary mediator of the resistance stage and via which axis is it released? Cortisol released via the hypothalamic pituitary adrenal axis. Question four. A patient with a ten year history of recurrent depression shows reduced hippocampal volume on MRI. What is the neurobiological mechanism linking chronic stress to this finding? Chronically elevated cortisol resulting from HPA axis dysregulation is neurotoxic to hippocampal neurons. Prolonged exposure leads to hippocampal atrophy, impairing memory, and increasing vulnerability to further depressive episodes. Finally, question five. What is the difference between a stressor and the stress response? A stressor is any stimulus that threatens homeostasis. The stress response is the body's physiological and psychological reaction aimed at restoring internal equilibrium. Let's summarize what we have learned today. Hancelia described the general adaptation syndrome, a three-stage model comprising the alarm stage, the resistance stage, and the exhaustion stage. Remember this via the mnemonic ARE. The HPA axis and cortisol are central to the resistance stage. Chronic HPA dysregulation is implicated in depression, PTSD, and hippocampal atrophy. Acute stress is adaptive. Chronic stress depletes physiological resources and carries significant psychiatric and physical risk. In our next episode, we explore the social origins of stress, including life events, daily hassles, and the Holmes and Rahe Social Readjustment Rating Scale. Thank you very much for listening to this episode of MRC Psych on the Go. Provision essential. I hope this episode helped to move your provision forward. If you have any questions or just want to continue the discussion, you can find me a link to MRC Psych on the Go. MRC MC on the goal.