⚡ Extreme Cold Conditions In Homeostasis
Disorders of arousal manifest Problems In Emaseo City a variety of ways, from barely audible mumbling, disoriented sleepwalking, to frantic bouts of shrieking Extreme Cold Conditions In Homeostasis flailing Extreme Cold Conditions In Homeostasis limbs Wills and Garcia, Retrieved The authors hypothesize that Extreme Cold Conditions In Homeostasis metabolism in emotional pathways with Extreme Cold Conditions In Homeostasis may increase emotional arousal and thereby adversely affect sleep Nofzinger et Extreme Cold Conditions In Homeostasis. The Sliding Filament Theory is to Extreme Cold Conditions In Homeostasis the sleep Extreme Cold Conditions In Homeostasis based on its symptoms while Ralpho Waldo Emerson: Stepping Outside Of Our Comfort Zone and treating the underlying medical or psychiatric disorder Petit et al. Some bats are true hibernators and rely upon a rapid, non-shivering thermogenesis of their brown fat deposit to bring Extreme Cold Conditions In Homeostasis out of hibernation.
Temperature Regulation Of The Human Body - Physiology - Biology - FuseSchool
The review also concluded that there was a lack of benefit in patients who had no daytime sleepiness Robinson et al. However, each of these studies was relatively small less than individuals , and findings can be considered only tentative. How does OSA cause sustained hypertension? During the night, the apneas and hypopneas of OSA cause a transient rise in blood pressure 30 mm Hg or more and increased activity of the sympathetic nervous system Figure Over time, the transient changes become more sustained and are detectable during the daytime, including evidence of sympathetic overactivity Narkiewicz and Somers, Studies have found that people with OSA versus those with similar blood pressure, but no OSA have faster heart rates, blunted heart rate variability, and increased blood pressure variability—all of which are markers of heightened cardiovascular risk Caples et al.
The precise pathophysiological steps from transient vascular changes to systemic hypertension are far from clear but may involve oxidative stress, upregulation of vasoactive substances Caples et al. Epidemiological studies reveal an association between OSA and cardiovascular disease, including arrhythmias Guilleminault et al. Most case-control studies detecting a relationship with myocardial infarction found adjusted odds ratios of around 4 Young et al. The adjusted OR for stroke was 1. A higher probability of stroke associated with OSA is also supported by other studies Bassetti and Aldrich, ; Parra et al.
In the Sleep Heart Health Study, apnea-hypopnea index was deter mined by polysomnography, and adjustments were made for a variety of confounding factors, including hypertension. That the hypertension adjustment did not eliminate the effect suggests that hypertension is not the exclusive means by which OSA may lead to cardiovascular disease. A limitation of cross-sectional and case-control analyses is that cause and effect cannot be determined: heart disease may have resulted in OSA or vice versa. However, an observational cohort study of 1, individuals, where 68 percent of individuals had OSA apnea-hypopnea index of 5 or higher , showed that OSA syndrome significantly increased the risk of stroke or death from any cause, and the increase is independent of other risk factors, including hypertension Yaggi et al.
Other studies have confirmed the risk of OSA syndrome with stroke or death from any cause Ayas et al. Furthermore, other large prospective studies also have shown an association between snoring—a marker for OSA—and incidence of cardiovascular diseases Jennum et al. As will be discussed in the next section, OSA is associated with glucose intolerance and diabetes, both of which are independent risk factors for cardiovascular disease. The events included myocardial infarction, stroke, and coronary artery bypass surgery. The untreated patients had refused CPAP but were followed regularly.
A second study found an increased mortality rate from cardiovascular disease in individuals who did not maintain CPAP treatment over a 5-year follow-up period Doherty et al. However, the number of new cases of cardiovascular disease was independent of CPAP treatment compliance. Although observational evidence of this type is not conclusive proof, because it may be subject to confounding by indication and other biases, it still lends weight to the strength of the association. Most studies finding elevated cardiovascular disease risk have been conducted in adults.
Whether or not children with sleep-disordered breathing are at risk for cardiovascular effects is not known. Children with OSA , as noted previously, do experience changes in blood pressure profiles, heart rate variability, and ventricular wall changes as measured by echocardiography Marcus et al. The paucity of longitudinal data on OSA in children, in whom levels of OSA may vary during growth and development and in whom responses to therapies such as tonsillectomy may be variable Morton et al.
Nonetheless, evidence that as many as 20 to 25 percent of children may have persistent OSA even after tonsillectomy underscores the potential importance of OSA as an early childhood risk factor for later cardiovascular diseases Amin et al. OSA is associated with impaired glucose tolerance and insulin resistance, according data from several studies Ip et al. Those outcomes were more prevalent in those with the highest apnea-hypopnea index. The study also found a relationship between sleep-related hypoxemia and glucose intolerance, which has implications for understanding mechanisms behind the OSA-glucose intolerance link see below.
The Sleep Heart Health Study, as noted earlier, was a large, cross-sectional, community-based study that used polysomnography to identify OSA. The analyses adjusted for obesity BMI and waist circumference , self-reported sleep duration, and other confounding factors. The findings suggest that OSA contributes to the onset of diabetes through the development of glucose intolerance and insulin resistance, which are established pathophysiological processes in diabetes Martin et al.
The study found that, after 10 years of follow-up, occasional snoring versus nonsnoring was associated with an elevated risk of new onset diabetes in women, and the risk was even greater for regular snoring Al-Delaimy et al. Regular or habitual snoring is an indicator of OSA. CPAP alleviates glucose intolerance in the short term and long term Brooks et al. The mechanisms by which OSA disrupts glucose metabolism are not established. Drawing on human studies and animal models, the biochemical cascade begins with intermittent hypoxia and recurrent sleep arousals sleep fragmentation. These events stimulate the sympathetic nervous system, hypothalamic-pituitary-adrenal axis, and adipocytes Punjabi and Beamer, Their activation, in turn, leads to release of catecholamines, cortisol, and inflammatory cytokines and other vasoactive intermediates, which may mediate the development of glucose intolerance, insulin resistance, and, ultimately, type 2 diabetes.
Because diabetes is also a risk factor for cardiovascular disease, the interrelationships may partly explain why OSA predisposes to cardiovascular disease Punjabi and Beamer, Up to 40 percent of people who are morbidly obese have OSA Vgontzas et al. This finding may reflect the role of obesity as a well-established risk factor for the development of OSA. It may also reflect obesity as a consequence of OSA, although the evidence is not yet conclusive Grunstein, b. Patients with newly diagnosed OSA, compared with controls matched for BMI and percent body fat, show recent weight gain Phillips et al. Data from the Wisconsin Sleep Cohort also show that individuals with OSA have reduced levels of physical activity; OSA-related sleepiness may contribute to changes in activity and energy expenditure, and thus contribute to weight gain.
OSA-related hormonal changes may also contribute to obesity. In general, patients with OSA have higher levels of leptin, the appetite-suppressing hormone Phillips et al. However, their morning levels are relatively lower than evening levels Patel et al. Furthermore, obesity also affects the severity of OSA. Significant weight loss in adolescents who underwent gastric bypass surgery mean, 58 kg was associated with a dramatic reduction of OSA severity Kalra et al.
In simplest terms, OSA is caused by narrowing or collapse of the airway as a result of anatomical and physiological abnormalities in pharyngeal structures. Apnea episodes cause hypoxemia insufficient oxygen in the blood and hypercapnia high concentration of blood carbon dioxide. The episodes also increase the output of the sympathetic nervous system Narkiewicz and Somers, , the effect of which is to restore pharyngeal muscle tone and reopen the airway. Although increased sympathetic activity is beneficial for restoring normal breathing and oxygen intake over the short term, it has long-term deleterious effects on vascular tone and blood pressure, among other effects Caples et al.
These early events—which are mediated by a variety of chemoreceptors in the carotid body and brainstem—trigger pathophysiological changes that occur not only during the obstructive apneas, but also extend into wakeful states during the day. For example, during daytime wakefulness, people with OSA have higher sympathetic activity Somers, et al. The full pathophysiology of OSA remains somewhat elusive, although research is piecing together the relationships between OSA and a range of the previously described long-term health effects.
The etiology of central sleep apnea, although also not well understood, is hypothesized to result from instability of respiratory control centers White, There are a number of risk factors for OSA , including:. Studies of patients at sleep clinics tend to show an association between sleep apnea and mortality He et al. The subgroup experienced twice the risk of mortality Lindberg et al. Other options, although less effective, include a variety of dental appliances Ferguson and Lowe, or surgery e. In children, the first-line treatment for most cases of OSA is adenotonsillectomy, according to clinical practice guidelines developed by the American Academy of Pediatrics Marcus et al.
Children who are not good candidates for this procedure can benefit from CPAP. Central apnea treatment is tailored to the cause of the ventilatory instability. Commonly used treatments include oxygen, CPAP, and acetazolamide, a drug that acts as a respiratory stimulant White, Insomnia is the most commonly reported sleep problem Ohayon, It is a highly prevalent disorder that often goes unrecognized and untreated despite its adverse impact on health and quality of life Benca, a see also Chapter 4.
The diagnostic criteria for primary insomnia include:. Insomnia symptoms are remarkably common, affecting at least 10 percent of adults in the United States Ford and Kamerow, ; Ohayon et al. Prevalence is higher among women and older individuals Mellinger et al. Severe insomnia tends to be chronic, with about 85 percent of patients continuing to report the same symptoms and impairment months or years after diagnosis Hohagen et al. The comorbidity of sleep disorders with psychiatric disorders is covered later in this chapter. The precise causes of insomnia are poorly understood but, in general terms, involve a combination of biological, psychological, and social factors. Insomnia is conceptualized as a state of hyperarousal Perlis et al.
Stress is thought to play a leading role in activating the hypothalamic-pituitary axis and setting the stage for chronic insomnia. A key study showed that adults with insomnia, compared with normal sleepers, have higher levels, over a hr period, of cortisol and adrenocorticotropic hormone ACTH , which are hormones released by the hypothalamic-pituitary-adrenal axis after stress exposure Vgontzas et al. The hour pattern of cortisol and ACTH secretion is different, however, from that in individuals who are chronically stressed.
Cognitive factors, such as worry, rumination, and fear of sleeplessness, perpetuate the problem through behavioral conditioning. Other perpetuating factors include light exposure and unstable sleep schedules Partinen and Hublin, Insomnia patients often attribute their difficulty sleeping to an overactive brain. Several lines of evidence, from preclinical to sleep neuroimaging studies in insomnia patients, suggest that there are multiple neural systems arranged hierarchically in the central nervous system that contribute to arousal as well as insomnia complaints. Disturbances in these systems may differ according to the nature of insomnia. Structures that regulate sleep and wakefulness, for example the brainstem, hypothalamus and basal forebrain, are abnormally overactive during sleep in primary insomnia patients Nofzinger et al.
In addition, limbic and paralimbic structures that regulate basic emotions and instinctual behaviors such as the amygdala, hippocampus, ventromedial prefrontal cortex and anterior cingulate cortex have been shown to be abnormally active during sleep in individuals with primary insomnia and secondary insomnias related to depression Nofzinger et al. Abnormal activity in neocortical structures that control executive function and are responsible for modulating behavior related to basic arousal and emotions has been observed in individuals with insomnias associated with depression Nofzinger et al.
The two main risk factors of insomnia are older age and female gender Edinger and Means, One large, population-based study found that insomnia was nearly twice as common in women than men, although reporting bias cannot be ruled out as a contributing factor Ford and Kamerow, The reason behind the apparent higher prevalence in women is not understood. Other risk factors for insomnia include family history of insomnia Dauvilliers et al. Although adolescent age is not viewed a risk factor, insomnia has rarely been studied in this age group. Insomnia is treatable with a variety of behavioral and pharmacological therapies, which may be used alone or in combination. While the therapies currently available to treat insomnia may provide benefit, the NIH State of the Science Conference on the Manifestations and Management of Chronic Insomnia concluded that more research and randomized clinical trials are needed to further verify their efficacy, particularly for long-term illness management and prevention of complications like depression NIH, Behavioral therapies appear as effective as pharmacological therapies Smith et al.
Behavioral therapies, according to a task force review of 48 clinical trials, benefit about 70 to 80 percent of patients for at least 6 months after completion of treatment Morin et al. The therapies are of several main types Table The major problem with current behavioral therapies is not their efficacy; rather it is lack of clinician awareness of their efficacy and lack of providers sufficiently trained and skilled in their use. Other problems are their cost and patient adherence Benca, a. The most efficacious pharmacological therapies for insomnia are hypnotic agents of two general types, benzodiazepine or nonbenzodiazepine hypnotics Nowell et al.
Nonbenzodiazepine hypnotics are advantageous because they generally have shorter half-lives, thus producing fewer impairments the next day, but the trade-off is that they may not be as effective at maintaining sleep throughout the night Morin, ; Benca, a. It is still unclear whether hypnotics lead to dependence. It is suggested that they should not be taken for more than 10 days in a row; however, recent studies suggest that hypnotics do not always lead to dependence Hajak et al. There have been no large-scale trials examining the safety and efficacy of hypnotics in children and adolescents. Other pharmacological classes used for insomnia include sedating antidepressants, antihistamines, and antipsychotics, but their efficacy and safety for treating insomnia have not been thoroughly studied Walsh et al.
Sleep disturbances are common features of psychiatric disorders. The most frequent types of sleep disturbances are insomnia, excessive daytime sleepiness hypersomnia , and parasomnia. Sleep disturbances are so commonly seen as symptoms of certain psychiatric disorders that they are listed as diagnostic criteria under DSM-IV APA, For example, insomnia is a symptom used with others to diagnose major depression.
The comorbidity, or coexistence, of a full-blown sleep disorder particularly insomnia and hypersomnia with a psychiatric disorder is also common. Forty percent of those diagnosed with insomnia, in a population-based study, also have a psychiatric disorder Ford and Kamerow, Among those diagnosed with hypersomnia, the prevalence of a psychiatric disorder is somewhat higher— The reasons behind the comorbidity of sleep and psychiatric disorders are not well understood.
Comorbidity might be due to one disorder being a risk factor or cause of the other; they might both be manifestations of the same or overlapping physiological disturbance; one might be a consequence of the other. In some cases, the sleep disturbance can be both cause and consequence. In generalized anxiety disorder, for example, the symptoms of fatigue and irritability used to diagnose it are often the result of a sleep disturbance, which itself is also a diagnostic symptom.
Adolescents with major depressive disorders report higher rates of sleep problems and, conversely, those with sleep difficulties report increased negative mood or mood regulation Ryan et al. In addition, sleep-onset abnormalities during adolescence have been associated with an increased risk of depression in later life Rao et al. The best studied and most prevalent comorbidity is insomnia with major depression. Insomnia as a symptom of depression is highly common. On the basis of longitudinal studies, insomnia is now established as a risk factor for major depression.
Not all people with insomnia have a depression diagnosis; however, studies have found that 15 to 20 percent of people diagnosed with insomnia have major depression Ford and Kamerow, ; Breslau et al. Depressed individuals have certain abnormalities detected by polysomnography. One is shorter rapid eye movement REM latency a shorter period of time elapsing from onset of sleep to onset of REM sleep , an effect that persists even after treatment for depression.
Shorter REM latency and slow-wave sleep SWS deficits tend to run in families; these abnormalities are also found in first-degree relatives of people with major depression, but who are unaffected by depression Giles et al. A variety of polysomnographic abnormalities have been found with other psychiatric disorders Benca, a. The etiological basis for the comorbidity of sleep disorders and psychiatric disorders is not well understood.
Most potential mechanisms for sleep changes in psychiatric disorders deal specifically with insomnia and depression. Possible mechanisms include neurotransmitter imbalance cholinergic-aminergic imbalance , circadian phase advance, and hypothalamic-pituitary-adrenal axis dysregulation Benca, a. Recent evidence implicating regions of the frontal lobe has emerged from imaging studies using positron emission tomography. As they progress from waking to non- REM NREM sleep, depressed subjects have smaller decreases in relative metabolism in regions of the frontal, parietal, and temporal cortex when compared to individuals who are healthy Nofzinger et al.
Normally, the transition from waking to NREM sleep is associated with decreases in these frontal lobe regions. What appears to occur with depression is that the decrease is less pronounced. Because the amygdala also plays a role in sleep regulation Jones, , this finding suggests that sleep and mood disorders may be manifestations of dysregulation in overlapping neurocircuits. The authors hypothesize that increased metabolism in emotional pathways with depression may increase emotional arousal and thereby adversely affect sleep Nofzinger et al.
A major problem is underdiagnosis and undertreatment of one or both of the comorbid disorders. One of the disorders may be missed or may be mistakenly dismissed as a condition that will recede once the other is treated. In the case of depression, for example, sleep abnormalities may continue once the depression episode has remitted Fava, If untreated, residual insomnia is a risk factor for depression recurrence Reynolds et al. Further, because sleep and psychiatric disorders, by themselves, are disabling, the treatment of the comorbidity may reduce needless disability. Insomnia , for example, worsens outcomes in depression, schizophrenia, and alcohol dependence. Another concern is that medication for one disorder might exacerbate the other e.
The choice of medica tion for psychiatric disorder or vice versa should be influenced by the nature of the sleep complaint e. As mentioned above insomnia is associated with depression, acting as both a risk factor and a manifestation Ford and Kamerow, ; Livingston et al. Several studies done were longitudinal in design, including one that tracked more than 1, male physicians for 40 years Chang et al. Another study, which followed 1, young adults at a health maintenance organization for 3. This figure is based on 16 percent of the sample who developed depression with a history of insomnia at baseline, as compared with 4. Insomnia is also a predictor of acute suicide among patients with mood disorders Fawcett et al.
Incidence of psychiatric disorders during 3. The striking association between insomnia and depression in so many studies suggests that insomnia is also an early marker for the onset of depression, and the two may be linked by a common pathophysiology. One hypothesis is that common pathways are the amygdala and other limbic structures of the brain Nofzinger et al. Another hypothesis is that chronic insomnia increases activity of the hypothalamic-pituitary-adrenal axis, which in turn contributes to depression Perlis et al.
The close association of insomnia and depression also raises the tantalizing possibility that treating insomnia may prevent some cases of depression Riemann and Voderholzer, , but limited data are available. The biological basis for the relationship between insomnia and new onset psychiatric disorders other than depression is also not known. Narcolepsy and idiopathic hypersomnia are characterized by a clinically significant complaint of excessive daytime sleepiness that is neither explained by a circadian sleep disorder, sleep-disordered breathing, or sleep deprivation, nor is it caused by a medical condition disturbing sleep AASM, Sleep logs or actigraphy a movement detector coupled with software that uses movement patterns to provide estimate sleep and wake times can also be used to exclude chronic sleep deprivation as a diagnosis prior to the MSLT.
In many cases narcolepsy arises during the mid to late teenage years; however, frequently initial diagnosis is not correct, resulting in delays in diagnosis of 15 to 25 years after the onset of symptoms Broughton et al. Onset of narcolepsy can also have a negative impact on school performance see Chapter 4. Narcolepsy is associated with a number of symptoms Anic-Labat et al. Clinical Laboratory Findings in Narcolepsy and Hypersomnia. It consists of five 20 minute daytime naps at 2-hour intervals. The amount of time it takes to fall asleep sleep more Idiopathic hypersomnia is classically separated into two subtypes.
The first, idiopathic hypersomnia with prolonged sleep time, is a rare disorder and is characterized by the following:. The second subtype of idiopathic hypersomnia, idiopathic hypersomnia without long sleep time, is characterized by a complaint of excessive daytime sleepiness and a short mean sleep latency on the MSLT. In most sleep disorders clinics with experience in this area, approximately one-third of hypersomnia cases are diagnosed with this condition Aldrich, The prevalence is estimated to be around 0. In contrast, the prevalence of idiopathic hypersomnia without prolonged sleep time may be more substantial, as most patients are likely not diagnosed Arand et al.
Recurrent hypersomnia is periodic either in synchrony with menstruation menstruation-linked periodic hypersomnia or without any association and mostly in males with Klein-Levin syndrome Billiard and Cadilhac, ; Arnulf et al. Klein-Levin syndrome is characterized by recurrent episodes of dramatic hypersomnia lasting from 2 days to several weeks. These episodes are associated with behavioral and cognitive abnormalities, binge eating or hypersexuality, and alternate with long asymptomatic periods that last months or years Arnulf et al. Narcolepsy and hypersomnia can affect children, adolescents, adults, and older persons. In most cases these disorders begin in adolescence. The prevalence of narcolepsy with definite cataplexy has been documented in adults by numerous population-based studies and occurs in 0.
In contrast, very little is known about the prevalence of narcolepsy without cataplexy. Recent studies using the MSLT indicate that approximately 3. Secondary cases of narcolepsy or hypersomnia are also common, but the overall prevalence is not known Table Similar to other sleep disorders, little is known about the pathophysiology and risk factors for narcolepsy and hypersomnia. Most of the knowledge in this area pertains to narcolepsy with cataplexy, which affects males and females equally.
Symptoms usually arise during adolescence. Approximately 70, hypothalamic neurons that are responsible for producing the neuropeptide hypocretin orexin are lost in individuals with narcolepsy with cataplexy Thannickal et al. Hypocretin is an excitatory neuropeptide that regulates the activity of other sleep regulatory networks. Consequently, in some cases low levels of hypocretin-1 in the CSF , may be used to diagnose narcolepsy Kanbayashi et al. Less is known regarding the pathophysiology of narcolepsy without cataplexy. The etiology is likely heterogeneous.
An unknown portion may be caused by partial or complete hypocretin deficiency Kanbayashi et al. However, it has been hypothesized that some individuals with partial cell loss may have normal CSF hypocretin-1 Mignot et al. The pathophysiology of idiopathic hypersomnia is unknown. When the disorder is associated with prolonged sleep time, it typically starts during adolescence and is lifelong. It is essential to exclude secondary causes, such as head trauma or hypersomnia owing to depression Roth, ; Billiard and Dauvilliers, Some cases with prolonged sleep times have been reported to be familial, suggesting a genetic origin. Even less is known about idiopathic hypersomnia with normal sleep time.
This condition is more variable and symptomatically defined. The cause of Kleine-Levin syndrome is unknown Arnulf et al. Treatment for these conditions is symptomatically based. Even in the case of narcolepsy in which the disorder is caused by hypocretin deficiency, current treatment does not aim at improving the defective neurotransmission Mignot et al. Behavioral measures, such as napping, support groups, and work arrangements are helpful but rarely sufficient.
In most cases, pharmacological treatment is needed Nishino and Mignot, ; Lammers and Overeem, However, as with other pharmaceuticals designed to treat sleep problems, large-scale clinical trails have not examined the efficacy and safety of drugs to treat narcolepsy in children and adolescents. In narcolepsy with cataplexy, pharmacological treatment for daytime sleepiness involves modafinil or amphetamine-like stimulants, which likely act through increasing dopamine transmission. Cataplexy and abnormal REM sleep symptoms, sleep paralysis and hallucinations, are typically treated with tricyclic antidepressants or serotonin and norepinephrine reuptake inhibitors.
Adrenergic reuptake inhibition is believed to be the primary mode of action. Sodium oxybate, or gamma hydroxybutyric acid, is also used at night to consolidate disturbed nocturnal sleep. This treatment is also effective on cataplexy and other symptoms. The treatment of narcolepsy without cataplexy and idiopathic hypersomnia uses similar compounds, most notably modafinil and amphetamine-like stimulants Billiard and Dauvilliers, Treatments, with the possible exception of lithium, of periodic hypersomnia and Kleine-Levin syndrome type are typically ineffective Arnulf et al.
Parasomnias are unpleasant or undesirable behaviors or experiences that occur during entry into sleep, during sleep, or during arousals from sleep AASM, They are categorized as primary parasomnias, which predominantly occur during the sleep state, and secondary parasomnias, which are complications associated with disorders of organ systems that occur during sleep. Primary parasomnias can further be classified depending on which sleep state they originate in, REM sleep, NREM , or others that can occur during either state Table Parasomnias typically manifest themselves during transition periods from one state of sleep to another, during which time the brain activity is reorganizing Mahowald and Schenck, Activities associated with parasomnias are characterized by being potentially violent or injurious, disruptive to other household members, resulting in excessive daytime sleepiness, or associated with medical, psychiatric, or neurological conditions Mahowald and Ettinger, Disorders of arousal are the most common type of parasomnia, occurring in as much as 4 percent of the adult population Ohayon et al.
Typically the arousals occur during the first 60 to 90 minutes of sleep and do not cause full awakenings, but rather partial arousal from deep NREM sleep. Disorders of arousal manifest in a variety of ways, from barely audible mumbling, disoriented sleepwalking, to frantic bouts of shrieking and flailing of limbs Wills and Garcia, Individuals who experience confusional arousals exhibit confused mental and behavioral activity following arousals from sleep. They are often disoriented in time and space, display slow speech, and blunted answers to questions AASM, Episodes of resistive and even violent behavior can last several minutes to hours.
Confusional arousals are more than three to four times more prevalent in children compared to individuals 15 years or older around 3 percent Ohayon et al. Sleepwalking is characterized by a complex series of behaviors that culminate in walking around with an altered state of consciousness and impaired judgment AASM, Individuals who are sleepwalking commonly perform routine and nonroutine behaviors at inappropriate times and have difficulty recalling episodic events. Like confusional arousals, the prevalence of sleepwalking is higher in children than adults AASM, There appears to be a genetic predisposition for sleepwalking. Children who have both parents affected by sleepwalking are 38 percent more likely to also be affected Klackenberg, ; Hublin et al.
Sleep terrors are characterized by arousal from SWS accompanied by a cry or piercing scream, in addition to autonomic nervous system and behavioral manifestations of intense fear AASM, Individuals with sleep terrors are typically hard to arouse from sleep and, when they are awoken, are confused and disoriented. There does not appear to be a significant gender or age difference in prevalence or incidence of sleep terrors AASM, REM sleep behavior disorder is characterized by a complex set of behaviors that occur during REM sleep, including mild to harmful body movements associated with dreams and nightmares AASM, The overall prevalence in the general population is estimated to be less than half a percent, slightly higher in older persons AASM, , and affecting men more frequently than women.
REM sleep behavior disorder is frequently associated with neurological disorders and it has been suggested that it could be an early sign of neurodegeneration Olson et al. There are a number of effective pharmacological treatments, including a long-acting benzodiazepine Schenck and Mahowald, , clonazepam Schenck et al. Nightmare disorder is characterized by recurrent disturbances of dreaming that are disturbing mental experiences that seem real and sometimes cause the individual to wake up. If awoken, individuals commonly have difficulty returning to sleep. Nightmares often occur during the second half of a normal period of sleep.
Dream content involves a distressing theme, typically imminent physical danger. During nightmares, individuals experience increased heart and respiration rates Fisher et al. Nightmares commonly affect children and adolescents and decrease in frequency and intensity as an individual grows older AASM, Drugs and alcohol can trigger nightmares. Prevalence rates are also higher in individuals suffering from acute stress disorder and posttraumatic stress disorder.
Individuals suffering from dementia commonly experience sleep abnormalities. Typically, sleep is more fragmented, leading to more awakenings and consequently less time asleep, and REM may be decreased Petit et al. These sleep impairments usually worsen as the disease progresses. Approximately one-quarter of these individuals have sleep disturbances Tractenberg et al. As a result of an increase in duration and number of awakenings, individuals spend an increased percentage of time in stage 1 sleep and a reduced percentage in stage 2 and SWS Prinz et al.
Associations with sleep disturbance and other behavioral symptoms have been identified, including aggressiveness Moran et al. However, the pathophysiology of this association is not known. Treatment options for demented individuals who suffer sleep disorders are typically the same as those received by individuals who do not have dementia. The approach is to address the sleep disorder based on its symptoms while managing and treating the underlying medical or psychiatric disorder Petit et al. It is characterized by trouble initiating walking and other movements, muscle tremor, a slow gait, and reduced facial expressions. During the day, many Parkinson patients have excessive sleepiness. Sleep disturbances typically increase with disease progression.
Individuals suffer from increased sleep latency and frequent awakenings, spending as much as 30 to 40 percent of the night awake Kales et al. This causes reduced time spent in stages 3 and 4 and REM sleep and increased duration in stages 1 and 2 Kales et al. Sleep patterns are affected by abnormalities caused by neurodegeneration in regions of the brain that are involved in regulating the sleep-wake cycle. Dopaminergic neurons in the substantia nigra are dramatically reduced in number, as are noradrenerics neurons in the locus coeruleus Jellinger, and cholinergic neurons in the pedunculopontine nucleus Zweig et al.
Braak and colleagues examined a large series of autopsy brains. The ability to ameliorate the symptoms of REM sleep behavioral disorder with dopaminergic agonist drugs suggests that it may be an early sign of damage to the dopaminergic system Trampus et al. When used in low doses, these medications can promote sleep, but high doses may cause increased nocturnal wakefulness, decreased SWS , and decreased sleep continuity Leeman et al. In contrast, excessive daytime sleepiness, including sleep attacks, has also been described in association with dopamine agonists Paus et al. All may potentially affect sleep Chrisp et al. Epilepsy refers to a group of various disorders characterized by abnormal electrical activity in the brain that manifests itself in individuals as a loss of or impaired consciousness and abnormal movements and behaviors.
Sleep, sleep deprivation, and seizure activity are tightly intertwined. It is estimated that sleep-related epilepsy may affect as many as 10 percent or more of epileptic individuals AASM, Sixty percent of individuals who suffer partial complex localization related seizures— Similarly, sleep and sleep deprivation increase the incidence of seizure activity. Sleep-related epilepsy normally presents with at least two of the following features: arousals, abrupt awakenings from sleep, generalized tonic-clonic movements of the limbs, focal limb movement, facial twitching, urinary incontinence, apnea, tongue biting, and postictal confusion and lethargy AASM, These features cause sleep fragmentation and daytime fatigue.
There are a number of common epileptic syndromes that manifest solely or predominately during the night, including nocturnal frontal lobe epilepsy, benign epilepsy of childhood with centrotemporal spikes, early-onset or late-onset childhood occipital epilepsy, juvenile myoclonic epilepsy, and continuous spike waves during non- REM sleep. Nocturnal frontal lobe epilepsy is characterized by severe sleep disruption, injuries caused by involuntary movements, and occasional daytime seizures.
Juvenile myoclonic epilepsy is characterized by synchronous involuntary muscle contractions that often occur during awakening. Continuous spike waves during non-REM sleep epilepsy are commonly associated with neurocognitive impairment and sometimes with impairment of muscle activity and control. Risk factors for sleep-related epilepsy include stress, sleep deprivation, other sleep disorders, and irregular sleep-wake rhythms. The etiologies for nocturnal seizures are not clearly understood. Genetic factors are likely important; however, as of yet no pathogenic markers have been associated with sleep-related epilepsy.
There are specific patterns of rhythmic activity among neurons within specific regions of the brain—the hypothalamus and brainstem—that regulate sleep and arousal. Association of specific neuronal activity between these different regions is important for regulating sleep, while bursts of disassociated neuronal activity may contribute to nocturnal seizures Tassinari et al. Treatments for seizures caused by sleep-related epileptic syndromes are typically similar to those of other seizure disorders Dreifuss and Porter, Individuals with epilepsy are susceptible to nocturnal sleep disturbance and daytime sleepiness associated with commonly used medications.
However, daytime hypersomnolence is not always treatable with antiepileptic drugs Palm et al. In particular, phenobarbital, a mainstay of treatment for many years, causes daytime sedation in a dose depen dent manner Brodie and Dichter, Daytime sedation is also observed with other antiepileptic agents including carbamazepine, alproate, phenytoin, and primidone. Some of the newer medication such as gabapentin, lamotrigine, bigabatrin, and zonisamide are often better tolerated Salinsky et al.
In addition to daytime sedation, these drugs also cause increased nocturnal sleep time. Vagal nerve stimulation, however, has been reported to improve daytime alertness Rizzo et al. Stroke results in a sudden loss of consciousness, sensation, and voluntary movement caused by disruption of blood flow—and therefore oxygen supply—to the brain. Insomnia is a common complication of stroke that may result from medication, inactivity, stress, depression, and brain damage. The annual incidence of stroke is 2 to 18 per individuals, and sleep-wake disturbances are found in at least 20 percent of stroke patients Bassetti, In addition, over 70 percent of individuals who have suffered a mild stroke and are under 75 years of age suffer fatigue Carlsson et al.
Risk factors for stroke include heart disease, hypertension, alcohol abuse, transient ischemic attacks, and, as described above, possibly sleep-disordered breathing Diaz and Sempere, Studies investigating the association between sleep-disordered breathing and stroke found that 60 to 70 percent of individuals who have suffered a stroke exhibit sleep-disordered breathing with an apnea-hypopnea index of 10 or greater Dyken et al.
Sleep-disordered breathing has also been found in a high frequency of individuals with transient ischemic attacks McArdle et al. There are no specific therapies that relieve sleep-related symptoms caused by a stroke. Rather, treatments depend on the specific symptoms and are similar to the treatments of sleep disorders that arise indepen dent of a stroke. For example, CPAP is the treatment of choice for sleep disordered breathing, and insomnia and parasomnias are treated using similar temporary hypnotic drug therapies as typically used, zolpidem or benzo-diazepines.
However, treatments for hypersomnia are not always as effective following a stroke Bassetti, The syndrome is currently the third most common cause of infant death in the United States CDC, , responsible for approximately 3, infant deaths a year in this country NICHD, b. Although there are no known causes for SIDS , various hypotheses exist about the mechanisms underlying the syndrome. Infants who later die of SIDS have higher heart rates, narrower heart rate ranges, and problems with coordination of respiration, heart rate, and arterial blood pressure while sleeping Kemp and Thach, ; Schechtman et al. This lack of coordination in the cardiorespiratory system may be a result of defects in the region of the brain responsible for controlling breathing and arousal Kinney et al.
The chief risk factor for SIDS is a prone sleeping position, otherwise known as stomach sleeping Dwyer et al. Vulnerability to SIDS seems to depend on both gender and ethnicity. Finally, general measures of poor health form the final category of risk factors. Smoking, drinking, or drug use by the mother during gestation are linked to an increased chance of SIDS -related deaths in infants, as is infant exposure to smoke Schoendorf and Kiely, ; AAP, ; Iyasu et al. A number of national intervention programs currently exist through various organizations. RLS is a neurological condition characterized by an irresistible urge to move the legs it also may affect the arms, trunk, or head and neck.
It is also associated with paresthesias—uncomfortable feelings—which individuals describe as creepy-crawly, jittery, itchy, or burning feelings. The symptoms are partially or completely relieved by movement. The urge to move and unpleasant sensations worsen during periods of rest or inactivity, espe cially in the evening and at night, causing most individuals difficulty falling asleep Michaud et al. The discomfort associated with RLS also causes individuals to wake frequently during the night Montplaisir et al. Individuals with RLS often experience periodic limb movements; however, periodic limb movement disorder see below is not always associated RLS Michaud et al.
This condition may be found in in adolescents and teenagers Kryger et al. RLS symptoms associated with pregnancy are caused by transient low levels of ferritin and folate; therefore, they typically disappear within 4 weeks after delivery Lee et al. In a cross-sectional survey of children, ADHD symptoms were almost twice as likely to occur with symptoms of RLS as would be expected by chance alone Chervin et al.
The exact cause of RLS is not completely understood. It likely results from altered dopamine and iron metabolism, and there is evidence for a genetic contribution. More than 50 percent of idiopathic cases are associated with a positive family history of RLS Ekbom, ; Walters et al. Susceptibility gene loci have been identified on chromosomes 12q Desautels et al. RLS commonly occurs in individuals with iron deficiency, including end-stage renal disease, iron-deficiency anemia, pregnancy, and gastric surgery. Iron deficiency, for example caused by repeated blood donation, may also be associated with RLS Silber et al.
It is hypothesized that low levels of iron impair transmission of dopamine signals, which contributes to RLS. Iron levels are reduced in the substantia nigra Allen et al. The iron deficiency is consistent with abnormal regulation of the transferrin receptor, which is responsible for transporting iron across cell membranes. Iron in turn is necessary for the synthesis of dopamine and the activity of the D 2 dopamine receptor Turjanski et al.
The association between dopamine, iron deficiency, and RLS is further supported by observations that dopamine antagonists usually make RLS symptoms worse Winkelmann et al. Idiopathic RLS is not associated with an increased mortality rate; however, in secondary cases of RLS, such as in individuals treated with long-term hemodialysis for end-stage renal disease, RLS is associated with a greater mortality risk Winkelman et al. There are both behavioral and pharmacological treatments for RLS ; however, there have been no clinical trials reporting the efficacy of non-pharmacological strategies to reduce RLS symptoms. Mild to moderate symptoms can sometimes be treated by lifestyle changes, including maintaining a normal sleeping pattern, taking supplements to manage iron deficiencies, and minimizing consumption of alcohol, caffeine, and tobacco NINDS, RLS is primarily treated using one of four classes of prescription medications: dopaminergic agents, benzodiazepines, opioids, or anticonvulsants central nervous system depressants.
Dopaminergic agents are the primary treatment option for individuals with RLS Hening et al. Medications include the dopamine precursor levodopa L-dopa. Although associated with some adverse effects, administration of L-dopa significantly reduces symptoms of RLS and periodic limb movements that occur throughout the night Brodeur et al. However, dopaminergic agents can also have a stimulating effect that may exacerbate insomnia. Benzodiazepines are effective in improving sleep continuity and are therefore frequently prescribed in combination with dopaminergic agents. Opioids may be prescribed in patients with severe symptoms to help to induce relaxation and minimize pain Walters et al. However, opioids may also exacerbate sleep apnea; therefore, they should be used cautiously in patients who snore Montplaisir et al.
Anticonvulsants are commonly prescribed as an alternative to dopaminergic agents, owing to their ability to minimize leg pain Montplaisir et al. It is believed that anticonvulsants, such as carbamazepine and gabapentin, are less potent than dopaminergic agents; however, there have been no comparative studies performed. Furthermore, there have been a limited number of studies that have examined the safety and efficacy of these treatments in children and adolescents. Periodic limb movement disorder is characterized by disruptions to sleep caused by periodic episodes of limb movements that occur during sleep, which cannot be explained by any other sleep disorder AASM, The periodic limb movements manifest themselves as rhythmic extensions of the big toe, dorsiflexions of the ankle, and occasional flexions of the knee and hip Coleman, These are scored using the periodic limb movements index, which examines over the course of an hour the number of movements that are 0.
An overnight index score of 5 or greater in children and 15 or greater in adults is considered pathogenic AASM, Periodic limb movements typically occur in the lower extremities and may result in autonomic arousal, cortical arousal, or an awakening. However, typically the individual is unaware of the movements. They are more frequent in the beginning of the night and cluster together. These events are associated with a fast heart rate, followed by a period of slow heart rate Friedland et al. Periodic limb movements disorder is associated with above average rates of depression, memory impairment, attention deficits, oppositional behaviors, and fatigue AASM, Periodic limb movements are believed to be very common, especially in older persons, occurring in 34 percent of individuals over the age of 60 AASM, However, the disorder—periodic limb movements associated with sleep disruption—is not as common.
Periodic limb movements are very common in RLS , occurring in 80 to 90 percent of individuals. It is also observed in individuals with narcolepsy, REM sleep behavior disorder Folstein et al. Sleep-disordered breathing may be a modulator that increases the association between periodic limb movements and ADHD Chervin and Archbold, These sleep problems often result from pain or infection associated with the primary condition.
Although these are both known to cause problems with sleep-wake cycles, as will be shown below, very little is still known about the etiology. Pain is described as an acute or chronic unpleasant sensory and emotional experience that varies from dull discomfort to unbearable agony that is associated with actual or potential tissue damage. The symptoms depend on the type and severity of the pain. They include daytime fatigue and sleepiness, poor sleep quality, delay in sleep onset, and decreased cognitive and motor performance Table Bonnet and Arand, Chronic pain affects at least 10 percent of the general adult population Harstall, , of whom 50 percent complain of poor sleep Atkinson et al.
There are a number of clinical pain conditions that individuals report affect their sleep quality— RLS , irritable bowel, gastric ulcer, cancer, musculoskeletal disorders, dental and orofacial pain, spinal cord damage, burns, and other trauma Lavigne et al. Although progress has been made, there are still many unanswered questions about how pain affects regions of the brain responsible for regulating the sleep-wake cycle. However, it is not known if hypocretin and other genes that regulate the circadian rhythms are affected by acute or chronic pain. Further, it is not known whether the hypothalamus, which is involved in sleep homeostasis, is affected by chronic pain Kshatri et al.
Because little is known about the interaction between pain and the circuitry in the brain that is responsible for regulating the sleep-wake cycle, much of the management of sleep problems focuses on managing and alleviating the pain or sleep quality. Infections caused by bacterial strains, viruses, and parasites may result in changes to sleep patterns. This is complicated by the unique effects that specific infections have on sleep patterns and the absence of a large body of clinical research. Alterations of sleep patterns can be affected by the type of bacterial infection Opp and Toth, For example, gram-negative bacteria induce enhanced sleep more rapidly than do gram-positive bacteria.
Differences in the process and progression of the disease also affect the sleep-wake cycle. Viral infections also have effects on the sleep-wake cycle. Individuals inoculated with rhinovirus or influenza virus report less sleep during the incubation period, while during the symptomatic period they slept longer Smith, However, compared to healthy individuals there were no reported difference in sleep quality and number of awakenings. The human immunodeficiency virus HIV also has been shown to alter sleep patterns. Individuals spend increased time in SWS during the second half of night Darko et al. As the infection progresses to AIDS, individuals develop increased sleep fragmentation, significant reductions in SWS, and disruption to the entire sleep architecture Norman et al.
Many patients with cancer also suffer pain or depression, which contributes to difficulty sleeping. When core temperature falls, the blood supply to the skin is reduced by intense vasoconstriction. The metabolic rate is increased, initially by non-shivering thermogenesis ,  followed by shivering thermogenesis if the earlier reactions are insufficient to correct the hypothermia. When core temperature rises are detected by thermoreceptors , the sweat glands in the skin are stimulated via cholinergic sympathetic nerves to secrete sweat onto the skin, which, when it evaporates, cools the skin and the blood flowing through it.
Panting is an alternative effector in many vertebrates, which cools the body also by the evaporation of water, but this time from the mucous membranes of the throat and mouth. Blood sugar levels are regulated within fairly narrow limits. The liver is inhibited from producing glucose , taking it up instead, and converting it to glycogen and triglycerides. The glycogen is stored in the liver, but the triglycerides are secreted into the blood as very low-density lipoprotein VLDL particles which are taken up by adipose tissue , there to be stored as fats.
The fat cells take up glucose through special glucose transporters GLUT4 , whose numbers in the cell wall are increased as a direct effect of insulin acting on these cells. The glucose that enters the fat cells in this manner is converted into triglycerides via the same metabolic pathways as are used by the liver and then stored in those fat cells together with the VLDL-derived triglycerides that were made in the liver. Muscle cells also take glucose up through insulin-sensitive GLUT4 glucose channels, and convert it into muscle glycogen. A fall in blood glucose, causes insulin secretion to be stopped, and glucagon to be secreted from the alpha cells into the blood. This inhibits the uptake of glucose from the blood by the liver, fats cells and muscle.
Instead the liver is strongly stimulated to manufacture glucose from glycogen through glycogenolysis and from non-carbohydrate sources such as lactate and de-aminated amino acids using a process known as gluconeogenesis. The glycogen stored in muscles remains in the muscles, and is only broken down, during exercise, to glucosephosphate and thence to pyruvate to be fed into the citric acid cycle or turned into lactate. It is only the lactate and the waste products of the citric acid cycle that are returned to the blood.
The liver can take up only the lactate, and by the process of energy consuming gluconeogenesis convert it back to glucose. Changes in the levels of oxygen, carbon dioxide, and plasma pH are sent to the respiratory center , in the brainstem where they are regulated. The partial pressure of oxygen and carbon dioxide in the arterial blood is monitored by the peripheral chemoreceptors PNS in the carotid artery and aortic arch. A change in the partial pressure of carbon dioxide is detected as altered pH in the cerebrospinal fluid by central chemoreceptors CNS in the medulla oblongata of the brainstem.
Information from these sets of sensors is sent to the respiratory center which activates the effector organs — the diaphragm and other muscles of respiration. An increased level of carbon dioxide in the blood, or a decreased level of oxygen, will result in a deeper breathing pattern and increased respiratory rate to bring the blood gases back to equilibrium. Too little carbon dioxide, and, to a lesser extent, too much oxygen in the blood can temporarily halt breathing, a condition known as apnea , which freedivers use to prolong the time they can stay underwater.
The partial pressure of carbon dioxide is more of a deciding factor in the monitoring of pH. With the lower level of carbon dioxide, to keep the pH at 7. The kidneys measure the oxygen content rather than the partial pressure of oxygen in the arterial blood. When the oxygen content of the blood is chronically low, oxygen-sensitive cells secrete erythropoietin EPO into the blood. The increase in RBCs leads to an increased hematocrit in the blood, and subsequent increase in hemoglobin that increases the oxygen carrying capacity. This is the mechanism whereby high altitude dwellers have higher hematocrits than sea-level residents, and also why persons with pulmonary insufficiency or right-to-left shunts in the heart through which venous blood by-passes the lungs and goes directly into the systemic circulation have similarly high hematocrits.
Regardless of the partial pressure of oxygen in the blood, the amount of oxygen that can be carried, depends on the hemoglobin content. The partial pressure of oxygen may be sufficient for example in anemia , but the hemoglobin content will be insufficient and subsequently as will be the oxygen content. Given enough supply of iron, vitamin B12 and folic acid , EPO can stimulate RBC production, and hemoglobin and oxygen content restored to normal.
The brain can regulate blood flow over a range of blood pressure values by vasoconstriction and vasodilation of the arteries. High pressure receptors called baroreceptors in the walls of the aortic arch and carotid sinus at the beginning of the internal carotid artery monitor the arterial blood pressure. This causes heart muscle cells to secrete the hormone atrial natriuretic peptide ANP into the blood. This acts on the kidneys to inhibit the secretion of renin and aldosterone causing the release of sodium, and accompanying water into the urine, thereby reducing the blood volume.
The arterioles are the main resistance vessels in the arterial tree , and small changes in diameter cause large changes in the resistance to flow through them. When the arterial blood pressure rises the arterioles are stimulated to dilate making it easier for blood to leave the arteries, thus deflating them, and bringing the blood pressure down, back to normal. At the same time, the heart is stimulated via cholinergic parasympathetic nerves to beat more slowly called bradycardia , ensuring that the inflow of blood into the arteries is reduced, thus adding to the reduction in pressure, and correction of the original error.
Low pressure in the arteries, causes the opposite reflex of constriction of the arterioles, and a speeding up of the heart rate called tachycardia. If the drop in blood pressure is very rapid or excessive, the medulla oblongata stimulates the adrenal medulla , via "preganglionic" sympathetic nerves , to secrete epinephrine adrenaline into the blood.
This hormone enhances the tachycardia and causes severe vasoconstriction of the arterioles to all but the essential organ in the body especially the heart, lungs, and brain. These reactions usually correct the low arterial blood pressure hypotension very effectively. The sensors for the second are the parafollicular cells in the thyroid gland. The parathyroid chief cells secrete parathyroid hormone PTH in response to a fall in the plasma ionized calcium level; the parafollicular cells of the thyroid gland secrete calcitonin in response to a rise in the plasma ionized calcium level.
The effector organs of the first homeostatic mechanism are the bones , the kidney , and, via a hormone released into the blood by the kidney in response to high PTH levels in the blood, the duodenum and jejunum. Parathyroid hormone in high concentrations in the blood causes bone resorption , releasing calcium into the plasma. This is a very rapid action which can correct a threatening hypocalcemia within minutes. High PTH concentrations cause the excretion of phosphate ions via the urine. Since phosphates combine with calcium ions to form insoluble salts see also bone mineral , a decrease in the level of phosphates in the blood, releases free calcium ions into the plasma ionized calcium pool. PTH has a second action on the kidneys. It stimulates the manufacture and release, by the kidneys, of calcitriol into the blood.
This steroid hormone acts on the epithelial cells of the upper small intestine, increasing their capacity to absorb calcium from the gut contents into the blood. The second homeostatic mechanism, with its sensors in the thyroid gland, releases calcitonin into the blood when the blood ionized calcium rises. This hormone acts primarily on bone, causing the rapid removal of calcium from the blood and depositing it, in insoluble form, in the bones. The two homeostatic mechanisms working through PTH on the one hand, and calcitonin on the other can very rapidly correct any impending error in the plasma ionized calcium level by either removing calcium from the blood and depositing it in the skeleton, or by removing calcium from it. The skeleton acts as an extremely large calcium store about 1 kg compared with the plasma calcium store about mg.
Longer term regulation occurs through calcium absorption or loss from the gut. The homeostatic mechanism which controls the plasma sodium concentration is rather more complex than most of the other homeostatic mechanisms described on this page. The sensor is situated in the juxtaglomerular apparatus of kidneys, which senses the plasma sodium concentration in a surprisingly indirect manner. Instead of measuring it directly in the blood flowing past the juxtaglomerular cells , these cells respond to the sodium concentration in the renal tubular fluid after it has already undergone a certain amount of modification in the proximal convoluted tubule and loop of Henle.
In response to a lowering of the plasma sodium concentration, or to a fall in the arterial blood pressure, the juxtaglomerular cells release renin into the blood. This decapeptide is known as angiotensin I. However, when the blood circulates through the lungs a pulmonary capillary endothelial enzyme called angiotensin-converting enzyme ACE cleaves a further two amino acids from angiotensin I to form an octapeptide known as angiotensin II. Angiotensin II is a hormone which acts on the adrenal cortex , causing the release into the blood of the steroid hormone , aldosterone. Angiotensin II also acts on the smooth muscle in the walls of the arterioles causing these small diameter vessels to constrict, thereby restricting the outflow of blood from the arterial tree, causing the arterial blood pressure to rise.
This, therefore, reinforces the measures described above under the heading of "Arterial blood pressure" , which defend the arterial blood pressure against changes, especially hypotension. The angiotensin II-stimulated aldosterone released from the zona glomerulosa of the adrenal glands has an effect on particularly the epithelial cells of the distal convoluted tubules and collecting ducts of the kidneys. Here it causes the reabsorption of sodium ions from the renal tubular fluid , in exchange for potassium ions which are secreted from the blood plasma into the tubular fluid to exit the body via the urine. The hyponatremia can only be corrected by the consumption of salt in the diet. However, it is not certain whether a "salt hunger" can be initiated by hyponatremia, or by what mechanism this might come about.
When the plasma sodium ion concentration is higher than normal hypernatremia , the release of renin from the juxtaglomerular apparatus is halted, ceasing the production of angiotensin II, and its consequent aldosterone-release into the blood. The kidneys respond by excreting sodium ions into the urine, thereby normalizing the plasma sodium ion concentration. The low angiotensin II levels in the blood lower the arterial blood pressure as an inevitable concomitant response.
The reabsorption of sodium ions from the tubular fluid as a result of high aldosterone levels in the blood does not, of itself, cause renal tubular water to be returned to the blood from the distal convoluted tubules or collecting ducts. This is because sodium is reabsorbed in exchange for potassium and therefore causes only a modest change in the osmotic gradient between the blood and the tubular fluid. Furthermore, the epithelium of the distal convoluted tubules and collecting ducts is impermeable to water in the absence of antidiuretic hormone ADH in the blood.
ADH is part of the control of fluid balance. Its levels in the blood vary with the osmolality of the plasma, which is measured in the hypothalamus of the brain. Aldosterone's action on the kidney tubules prevents sodium loss to the extracellular fluid ECF. However, low aldosterone levels cause a loss of sodium ions from the ECF, which could potentially cause a change in extracellular osmolality and therefore of ADH levels in the blood. High potassium concentrations in the plasma cause depolarization of the zona glomerulosa cells' membranes in the outer layer of the adrenal cortex.
Aldosterone acts primarily on the distal convoluted tubules and collecting ducts of the kidneys, stimulating the excretion of potassium ions into the urine. The total amount of water in the body needs to be kept in balance. Fluid balance involves keeping the fluid volume stabilized, and also keeping the levels of electrolytes in the extracellular fluid stable. Fluid balance is maintained by the process of osmoregulation and by behavior. Osmotic pressure is detected by osmoreceptors in the median preoptic nucleus in the hypothalamus. Measurement of the plasma osmolality to give an indication of the water content of the body, relies on the fact that water losses from the body, through unavoidable water loss through the skin which is not entirely waterproof and therefore always slightly moist, water vapor in the exhaled air , sweating , vomiting , normal feces and especially diarrhea are all hypotonic , meaning that they are less salty than the body fluids compare, for instance, the taste of saliva with that of tears.
The latter has almost the same salt content as the extracellular fluid, whereas the former is hypotonic with respect to the plasma. Saliva does not taste salty, whereas tears are decidedly salty. Nearly all normal and abnormal losses of body water therefore cause the extracellular fluid to become hypertonic. Conversely, excessive fluid intake dilutes the extracellular fluid causing the hypothalamus to register hypotonic hyponatremia conditions. When the hypothalamus detects a hypertonic extracellular environment, it causes the secretion of an antidiuretic hormone ADH called vasopressin which acts on the effector organ, which in this case is the kidney. The effect of vasopressin on the kidney tubules is to reabsorb water from the distal convoluted tubules and collecting ducts , thus preventing aggravation of the water loss via the urine.
The hypothalamus simultaneously stimulates the nearby thirst center causing an almost irresistible if the hypertonicity is severe enough urge to drink water. The cessation of urine flow prevents the hypovolemia and hypertonicity from getting worse; the drinking of water corrects the defect. Hypo-osmolality results in very low plasma ADH levels. This results in the inhibition of water reabsorption from the kidney tubules, causing high volumes of very dilute urine to be excreted, thus getting rid of the excess water in the body. Urinary water loss, when the body water homeostat is intact, is a compensatory water loss, correcting any water excess in the body. However, since the kidneys cannot generate water, the thirst reflex is the all-important second effector mechanism of the body water homeostat, correcting any water deficit in the body.
The plasma pH can be altered by respiratory changes in the partial pressure of carbon dioxide; or altered by metabolic changes in the carbonic acid to bicarbonate ion ratio. The bicarbonate buffer system regulates the ratio of carbonic acid to bicarbonate to be equal to , at which ratio the blood pH is 7. A change in the plasma pH gives an acid—base imbalance. In acid—base homeostasis there are two mechanisms that can help regulate the pH. Respiratory compensation a mechanism of the respiratory center , adjusts the partial pressure of carbon dioxide by changing the rate and depth of breathing, to bring the pH back to normal. The partial pressure of carbon dioxide also determines the concentration of carbonic acid, and the bicarbonate buffer system can also come into play.
Renal compensation can help the bicarbonate buffer system. The sensor for the plasma bicarbonate concentration is not known for certain. It is very probable that the renal tubular cells of the distal convoluted tubules are themselves sensitive to the pH of the plasma. Bicarbonate ions are simultaneously secreted into the blood that decreases the carbonic acid, and consequently raises the plasma pH. When hydrogen ions are excreted into the urine, and bicarbonate into the blood, the latter combines with the excess hydrogen ions in the plasma that stimulated the kidneys to perform this operation. The resulting reaction in the plasma is the formation of carbonic acid which is in equilibrium with the plasma partial pressure of carbon dioxide.
This is tightly regulated to ensure that there is no excessive build-up of carbonic acid or bicarbonate. The overall effect is therefore that hydrogen ions are lost in the urine when the pH of the plasma falls. The concomitant rise in the plasma bicarbonate mops up the increased hydrogen ions caused by the fall in plasma pH and the resulting excess carbonic acid is disposed of in the lungs as carbon dioxide. This restores the normal ratio between bicarbonate and the partial pressure of carbon dioxide and therefore the plasma pH. The converse happens when a high plasma pH stimulates the kidneys to secrete hydrogen ions into the blood and to excrete bicarbonate into the urine.
The hydrogen ions combine with the excess bicarbonate ions in the plasma, once again forming an excess of carbonic acid which can be exhaled, as carbon dioxide, in the lungs, keeping the plasma bicarbonate ion concentration, the partial pressure of carbon dioxide and, therefore, the plasma pH, constant. Cerebrospinal fluid CSF allows for regulation of the distribution of substances between cells of the brain,  and neuroendocrine factors, to which slight changes can cause problems or damage to the nervous system. For example, high glycine concentration disrupts temperature and blood pressure control, and high CSF pH causes dizziness and syncope.
Inhibitory neurons in the central nervous system play a homeostatic role in the balance of neuronal activity between excitation and inhibition. Inhibitory neurons using GABA , make compensating changes in the neuronal networks preventing runaway levels of excitation. The neuroendocrine system is the mechanism by which the hypothalamus maintains homeostasis, regulating metabolism , reproduction, eating and drinking behaviour, energy utilization, osmolarity and blood pressure. The regulation of metabolism, is carried out by hypothalamic interconnections to other glands. Two other regulatory endocrine axes are the hypothalamic—pituitary—adrenal axis HPA axis and the hypothalamic—pituitary—thyroid axis HPT axis.
The liver also has many regulatory functions of the metabolism. An important function is the production and control of bile acids. Too much bile acid can be toxic to cells and its synthesis can be inhibited by activation of FXR a nuclear receptor. At the cellular level, homeostasis is carried out by several mechanisms including transcriptional regulation that can alter the activity of genes in response to changes. The amount of energy taken in through nutrition needs to match the amount of energy used.
To achieve energy homeostasis appetite is regulated by two hormones, grehlin and leptin. Grehlin stimulates hunger and the intake of food and leptin acts to signal satiety fullness. A review of weight-change interventions, including dieting , exercise and overeating, found that body weight homeostasis could not precisely correct for "energetic errors", the loss or gain of calories, in the short-term. Many diseases are the result of a homeostatic failure. Almost any homeostatic component can malfunction either as a result of an inherited defect , an inborn error of metabolism , or an acquired disease. Some homeostatic mechanisms have inbuilt redundancies, which ensures that life is not immediately threatened if a component malfunctions; but sometimes a homeostatic malfunction can result in serious disease, which can be fatal if not treated.
A well-known example of a homeostatic failure is shown in type 1 diabetes mellitus. Here blood sugar regulation is unable to function because the beta cells of the pancreatic islets are destroyed and cannot produce the necessary insulin. The blood sugar rises in a condition known as hyperglycemia. The abnormally high plasma ionized calcium concentrations cause conformational changes in many cell-surface proteins especially ion channels and hormone or neurotransmitter receptors  giving rise to lethargy, muscle weakness, anorexia, constipation and labile emotions. The body water homeostat can be compromised by the inability to secrete ADH in response to even the normal daily water losses via the exhaled air, the feces , and insensible sweating.
On receiving a zero blood ADH signal, the kidneys produce huge unchanging volumes of very dilute urine, causing dehydration and death if not treated. As organisms age, the efficiency of their control systems becomes reduced. The inefficiencies gradually result in an unstable internal environment that increases the risk of illness, and leads to the physical changes associated with aging.
Various chronic diseases are kept under control by homeostatic compensation, which masks a problem by compensating for it making up for it in another way. However, the compensating mechanisms eventually wear out or are disrupted by a new complicating factor such as the advent of a concurrent acute viral infection , which sends the body reeling through a new cascade of events. Such decompensation unmasks the underlying disease, worsening its symptoms.
Common examples include decompensated heart failure , kidney failure , and liver failure. In the Gaia hypothesis , James Lovelock  stated that the entire mass of living matter on Earth or any planet with life functions as a vast homeostatic superorganism that actively modifies its planetary environment to produce the environmental conditions necessary for its own survival. In this view, the entire planet maintains several homeostasis the primary one being temperature homeostasis.
Whether this sort of system is present on Earth is open to debate. However, some relatively simple homeostatic mechanisms are generally accepted. For example, it is sometimes claimed that when atmospheric carbon dioxide levels rise, certain plants may be able to grow better and thus act to remove more carbon dioxide from the atmosphere. However, warming has exacerbated droughts, making water the actual limiting factor on land.
When sunlight is plentiful and the atmospheric temperature climbs, it has been claimed that the phytoplankton of the ocean surface waters, acting as global sunshine, and therefore heat sensors, may thrive and produce more dimethyl sulfide DMS. The DMS molecules act as cloud condensation nuclei , which produce more clouds, and thus increase the atmospheric albedo , and this feeds back to lower the temperature of the atmosphere.
However, rising sea temperature has stratified the oceans, separating warm, sunlit waters from cool, nutrient-rich waters. Thus, nutrients have become the limiting factor, and plankton levels have actually fallen over the past 50 years, not risen. As scientists discover more about Earth, vast numbers of positive and negative feedback loops are being discovered, that, together, maintain a metastable condition, sometimes within a very broad range of environmental conditions.
Predictive homeostasis is an anticipatory response to an expected challenge in the future, such as the stimulation of insulin secretion by gut hormones which enter the blood in response to a meal. An actuary may refer to risk homeostasis , where for example people who have anti-lock brakes have no better safety record than those without anti-lock brakes, because the former unconsciously compensate for the safer vehicle via less-safe driving habits.
Previous to the innovation of anti-lock brakes, certain maneuvers involved minor skids, evoking fear and avoidance: Now the anti-lock system moves the boundary for such feedback, and behavior patterns expand into the no-longer punitive area. It has also been suggested that ecological crises are an instance of risk homeostasis in which a particular behavior continues until proven dangerous or dramatic consequences actually occur. Sociologists and psychologists may refer to stress homeostasis , the tendency of a population or an individual to stay at a certain level of stress , often generating artificial stresses if the "natural" level of stress is not enough.
From Wikipedia, the free encyclopedia. Not to be confused with hemostasis. State of steady internal conditions maintained by living things. Index Outline Glossary. Key components. Biologist list List of biology awards List of journals List of research methods List of unsolved problems. Agricultural science Biomedical sciences Health technology Pharming. Main articles: Thermoregulation and Thermoregulation in humans. Further information: Preoptic area. Main article: Human iron metabolism. This section needs expansion. You can help by adding to it. November April Main articles: Respiratory center and Gas exchange.Familial and probably genetic factors strongly contribute to OSA Extreme Cold Conditions In Homeostasis et al. These require treatment as in other patients with pain or depression as causes of insomnia. Sleep loss and sleep disorders are Franklin D. Roosevelt: The Civilian Conservation Corps the most common yet frequently overlooked and readily treatable health problems. The reason behind the Extreme Cold Conditions In Homeostasis higher prevalence Extreme Cold Conditions In Homeostasis women is not understood. Millan MJ. In children, the main risk factor for OSA is tonsillar Extreme Cold Conditions In Homeostasis, although OSA Extreme Cold Conditions In Homeostasis also occur in children with congenital and neuromuscular disorders and in Success Profiler Reflection who were born prematurely Rosen et al.