Chapter 9

A key stress hormone relationship is the regulation of the __-__- __ (HPA) system. In sequence, the perception of stress activates the __ to secrete __-releasing hormone (CRH), which binds to specific receptors on anterior __ cells that, in turn, produce __ hormone (ACTH). ACTH is then transported through the blood to the __ glands located on the top of the kidneys. After binding to specific receptors on the cortex of the adrenal glands, __ hormones (primarily __) are released.

A key stress hormone relationship is the regulation of the hypothalamic-pituitary- adrenal (HPA) system. In sequence, the perception of stress activates the hypothalamus to secrete corticotropin-releasing hormone (CRH), which binds to specific receptors on anterior pituitary cells that, in turn, produce adrenocorticotropic hormone (ACTH). ACTH is then transported through the blood to the adrenal glands located on the top of the kidneys. After binding to specific receptors on the cortex of the adrenal glands, glucocorticoid hormones (primarily cortisol) are released.

Another important adaptive function of cortisol is to enhance __ during acute stress. Cortisol exerts beneficial effects by inhibiting initial __ effects, for example, vasodilation and increased capillary permeability. Cortisol also promotes __ and __. These actions are mainly accomplished by facilitating the effects of glucocorticoid receptor (GR), namely, the transcription of genetic material (through DNA binding) within leukocytes.

Another important adaptive function of cortisol is to enhance immunity during acute stress. Cortisol exerts beneficial effects by inhibiting initial inflammatory effects, for example, vasodilation and increased capillary permeability. Cortisol also promotes resolution and repair. These actions are mainly accomplished by facilitating the effects of glucocorticoid receptor (GR), namely, the transcription of genetic material (through DNA binding) within leukocytes.

autonomic nervous system sympathetic nervous system Because __ sympathetic fibers are all myelinated, travel to the adrenal medulla is quick, and innervation causes the rapid release of epinephrine and norepinephrine. __ and __ are mediators of the fight or flight response

Because preganglionic sympathetic fibers are all myelinated, travel to the adrenal medulla is quick, and innervation causes the rapid release of epinephrine and norepinephrine. Epinephrine and norepinephrine are mediators of the fight or flight response

Chronic dysregulation of the HPA axis, especially abnormal elevated levels of __, has been linked to a wide variety of disorders, including obesity, sleep deprivation, lipid abnormalities, hypertension, diabetes, atherosclerosis, and loss of bone density. In the brain, chronic glucocorticoid secretion may reduce __ volume, enlarge the ventricles, and modulate reversible cortical atrophy.1,24 These CNS changes may contribute to cognitive impairments and emotional disorders.

Chronic dysregulation of the HPA axis, especially abnormal elevated levels of cortisol, has been linked to a wide variety of disorders, including obesity, sleep deprivation, lipid abnormalities, hypertension, diabetes, atherosclerosis, and loss of bone density. In the brain, chronic glucocorticoid secretion may reduce hippocampal volume, enlarge the ventricles, and modulate reversible cortical atrophy.1,24 These CNS changes may contribute to cognitive impairments and emotional disorders.

Cortisol also affects __ metabolism. It has an anabolic effect by increasing the rate of __ synthesis and __ acid (RNA) in the __. This is countered by its catabolic effect on __ stores in other tissues. Protein __ acts to increase levels of circulating amino acids; therefore chronic exposure to excess cortisol can severely deplete __ stores in muscle, bone, connective tissue, and skin.

Cortisol also affects protein metabolism. It has an anabolic effect by increasing the rate of protein synthesis and ribonucleic acid (RNA) in the liver. This is countered by its catabolic effect on protein stores in other tissues. Protein catabolism acts to increase levels of circulating amino acids; therefore chronic exposure to excess cortisol can severely deplete protein stores in muscle, bone, connective tissue, and skin.

Cortisol mobilizes substances needed for cellular metabolism and stimulates __ or the formation of __ from non-carbohydrate sources, such as amino acids or free fatty acids in the liver. In addition, cortisol enhances the elevation of blood __ levels that is promoted by other hormones, such as e__, g__, and growth hormone. Cortisol also __ the uptake and oxidation of glucose by many body cells. Overall, cortisol's actions on carbohydrate metabolism result in increased blood __ levels, thereby energizing the body to combat the stressor.

Cortisol mobilizes substances needed for cellular metabolism and stimulates gluconeogenesis or the formation of glucose from non-carbohydrate sources, such as amino acids or free fatty acids in the liver. In addition, cortisol enhances the elevation of blood glucose levels that is promoted by other hormones, such as epinephrine, glucagon, and growth hormone. Cortisol also inhibits the uptake and oxidation of glucose by many body cells. Overall, cortisol's actions on carbohydrate metabolism result in increased blood glucose levels, thereby energizing the body to combat the stressor.

Cortisol secretion during stress exerts beneficial effects by inhibiting initial __ effects, for example, vasodilation and increased capillary permeability. Cortisol also promotes __ and __. These actions are mainly accomplished by facilitating the effects of glucocorticoid receptor (GR), namely, the transcription of genetic material (through DNA binding) within __. Because glucocorticoids are so widely expressed, they influence virtually all __ cells. The adaptiveness or destructiveness of cortisol-induced effects may depend on the intensity, type, and duration of the __; the tissue involved; and the subsequent concentration and length of cortisol exposure. Finally, glucocorticoids have been shown to induce T-cell __.

Cortisol secretion during stress exerts beneficial effects by inhibiting initial inflammatory effects, for example, vasodilation and increased capillary permeability. Cortisol also promotes resolution and repair. These actions are mainly accomplished by facilitating the effects of glucocorticoid receptor (GR), namely, the transcription of genetic material (through DNA binding) within leukocytes. Because glucocorticoids are so widely expressed, they influence virtually all immune cells. The adaptiveness or destructiveness of cortisol-induced effects may depend on the intensity, type, and duration of the stressor; the tissue involved; and the subsequent concentration and length of cortisol exposure. Finally, glucocorticoids have been shown to induce T-cell apoptosis.

During stress, the secretion of glucocorticoid hormones, primarily __ (cortisol is known outside the body as hydrocortisone), reaches __ tissues, including the brain, easily penetrates cell __, and reacts with numerous intracellular glucocorticoid receptors (see Figure 9-3). Because they spare almost no tissue or organ and influence a large proportion of the human genome, glucocorticoids exert significant __ biologic actions.24 They regulate many functions of the __, including arousal, cognition, mood, sleep, metabolism, maintenance of cardiovascular tone, the immune and inflammatory reaction, and growth and reproduction.

During stress, the secretion of glucocorticoid hormones, primarily cortisol (cortisol is known outside the body as hydrocortisone), reaches all tissues, including the brain, easily penetrates cell membranes, and reacts with numerous intracellular glucocorticoid receptors (see Figure 9-3). Because they spare almost no tissue or organ and influence a large proportion of the human genome, glucocorticoids exert significant diverse biologic actions.24 They regulate many functions of the CNS, including arousal, cognition, mood, sleep, metabolism, maintenance of cardiovascular tone, the immune and inflammatory reaction, and growth and reproduction.

In 1946, Hans __ further popularized and advanced the concept of __ in terms of a chemical or physical change (i.e., physiologic stress, in response either to the __ environment or within the __ itself). His work showed that physiologic stress involved: (1) enlargement of the __ gland, (2) decreased __ levels in the blood from damage to __ structures of the immune system, and (3) development of bleeding __ in the stomach and __ lining. Selye concluded physiologic stress will impair the ability of the organism to resist __ stressors and represented the hallmark pattern of a nonspecific stress response that was labeled the __ __ __ (__).

In 1946, Hans Selye further popularized and advanced the concept of stress in terms of a chemical or physical change (i.e., physiologic stress, in response either to the external environment or within the body itself). His work showed that physiologic stress involved: (1) enlargement of the adrenal gland, (2) decreased lymphocyte levels in the blood from damage to lymphatic structures of the immune system, and (3) development of bleeding ulcers in the stomach and duodenal lining. Selye concluded physiologic stress will impair the ability of the organism to resist future stressors and represented the hallmark pattern of a nonspecific stress response that was labeled the general adaptation syndrome (GAS).

In emergency situations, a generalized and widespread discharge of the __ system occurs and is known as the "__ or __" reflex or acute stress response (see Chapter 9). This is accomplished by an increased firing frequency of __ fibers and by activation of __ fibers normally silent and at rest (fibers to the sweat glands, pilomotor muscles, and the adrenal medulla, as well as vasodilator fibers to muscle). Regulation of __ tone is considered the single most important function of the sympathetic nervous system.

In emergency situations, a generalized and widespread discharge of the sympathetic system occurs and is known as the "fight or flight" reflex or acute stress response (see Chapter 9). This is accomplished by an increased firing frequency of sympathetic fibers and by activation of sympathetic fibers normally silent and at rest (fibers to the sweat glands, pilomotor muscles, and the adrenal medulla, as well as vasodilator fibers to muscle). Regulation of vasomotor tone is considered the single most important function of the sympathetic nervous system.

In the periphery, heightened stress-induced __ levels promote gastric secretion in the stomach and intestines, potentially causing gastric __, which may account for the gastrointestinal __ observed by Selye. Furthermore, glucocorticoids contribute to the development of metabolic syndrome and the pathogenesis of __ by directly causing insulin resistance and influencing genetic variations that predispose to obesity.

In the periphery, heightened stress-induced cortisol levels promote gastric secretion in the stomach and intestines, potentially causing gastric ulcers, which may account for the gastrointestinal ulceration observed by Selye. Furthermore, glucocorticoids contribute to the development of metabolic syndrome and the pathogenesis of obesity by directly causing insulin resistance and influencing genetic variations that predispose to obesity.

Increased parasympathetic activity promotes __ and __ and is characterized by reduced heart rate and enhanced visceral functions concerned with digestion. Stimulation of the __ nerve (cranial nerve __) in the gastrointestinal tract increases __ and secretion, as well as the relaxation of sphincters. Activation of parasympathetic fibers in the head, provided by cranial nerves __, __, and __, causes constriction of the pupil, tear secretion, and increased salivary secretion. Stimulation of the sacral division of the parasympathetic system __ the urinary bladder and facilitates the process of genital erection.

Increased parasympathetic activity promotes rest and tranquility and is characterized by reduced heart rate and enhanced visceral functions concerned with digestion. Stimulation of the vagus nerve (cranial nerve X) in the gastrointestinal tract increases peristalsis and secretion, as well as the relaxation of sphincters. Activation of parasympathetic fibers in the head, provided by cranial nerves III, VII, and IX, causes constriction of the pupil, tear secretion, and increased salivary secretion. Stimulation of the sacral division of the parasympathetic system contracts the urinary bladder and facilitates the process of genital erection.

Many body organs are innervated by both the sympathetic and parasympathetic nervous systems. The two divisions often cause __ responses; for example, sympathetic stimulation of the stomach causes decreased __, whereas parasympathetic stimulation of the intestine increases __. In general, sympathetic stimulation promotes responses for the __ of the individual. For example, sympathetic activity increases blood glucose levels and __ and raises the __ pressure.

Many body organs are innervated by both the sympathetic and parasympathetic nervous systems. The two divisions often cause opposite responses; for example, sympathetic stimulation of the stomach causes decreased peristalsis, whereas parasympathetic stimulation of the intestine increases peristalsis. In general, sympathetic stimulation promotes responses for the protection of the individual. For example, sympathetic activity increases blood glucose levels and temperature and raises the blood pressure.

autonomic nervous system Anatomy of the Parasympathetic Nervous System Parasympathetic nerves arising from nuclei in the brainstem travel to the viscera of the head, thorax, and abdomen within cranial nerves—including the oculomotor (__), facial (__), glossopharyngeal (__), and vagus (__) nerves.

Parasympathetic nerves arising from nuclei in the brainstem travel to the viscera of the head, thorax, and abdomen within cranial nerves—including the oculomotor (III), facial (VII), glossopharyngeal (IX), and vagus (X) nerves.

autonomic nervous system Anatomy of the Parasympathetic Nervous System Preganglionic parasympathetic nerves that originate from the __ region of the spinal cord run either separately or together with some spinal nerves. The preganglionic axons unite to form the __ nerve, which innervates the viscera of the pelvic cavity. These preganglionic axons synapse with postganglionic neurons in terminal ganglia located close to the organs they innervate.

Preganglionic parasympathetic nerves that originate from the sacral region of the spinal cord run either separately or together with some spinal nerves. The preganglionic axons unite to form the pelvic nerve, which innervates the viscera of the pelvic cavity. These preganglionic axons synapse with postganglionic neurons in terminal ganglia located close to the organs they innervate

autonomic nervous system sympathetic nervous system Some preganglionic axons form pathways called __ nerves, which lead to __ ganglia on the front of the aorta. The __ ganglia are named according to the branches of the aorta nearest them, namely, the celiac, superior mesenteric, and inferior mesenteric. The preganglionic neurons synapse with postganglionic neurons within the collateral ganglia. These postganglionic neurons leave the collateral ganglia and innervate the viscera below the diaphragm.

Some preganglionic axons form pathways called splanchnic nerves, which lead to collateral ganglia on the front of the aorta. The collateral ganglia are named according to the branches of the aorta nearest them, namely, the celiac, superior mesenteric, and inferior mesenteric. The preganglionic neurons synapse with postganglionic neurons within the collateral ganglia. These postganglionic neurons leave the collateral ganglia and innervate the viscera below the diaphragm

autonomic nervous system Neurotransmitters and Neuroreceptors Sympathetic preganglionic fibers and parasympathetic preganglionic and postganglionic fibers release __—the same neurotransmitter released by somatic efferent neurons (see Figure 13-26). These fibers are characterized by cholinergic transmission. Most postganglionic sympathetic fibers release __ (__) and thus are considered to function by __ transmission. A few postganglionic sympathetic fibers, such as those that innervate the sweat glands, release __.

Sympathetic preganglionic fibers and parasympathetic preganglionic and postganglionic fibers release acetylcholine—the same neurotransmitter released by somatic efferent neurons (see Figure 13-26). These fibers are characterized by cholinergic transmission. Most postganglionic sympathetic fibers release norepinephrine (adrenaline) and thus are considered to function by adrenergic transmission. A few postganglionic sympathetic fibers, such as those that innervate the sweat glands, release acetylcholine.

The ANS coordinates and maintains a steady state among __ (internal) organs, such as regulation of cardiac muscle, smooth muscle, and the glands of the body. This system is considered an __ system because one generally cannot will these functions to happen. The ANS is separated both structurally and functionally into two divisions: (1) the __ nervous system and (2) the __ nervous system

The ANS coordinates and maintains a steady state among visceral (internal) organs, such as regulation of cardiac muscle, smooth muscle, and the glands of the body. This system is considered an involuntary system because one generally cannot will these functions to happen. The ANS is separated both structurally and functionally into two divisions: (1) the sympathetic nervous system and (2) the parasympathetic nervous system

The GAS involved three successive stages: the __, the __ or __, and the __ stages.

The GAS involved three successive stages: the alarm, the resistance or adaptation, and the exhaustion stages.

autonomic nervous system Neurotransmitters and Neuroreceptors The action of __ varies with the type of neuroreceptor stimulated. It should be remembered that catecholamines also are released by the adrenal medulla gland that physiologically and biochemically resembles the __ nervous system. Two types of adrenergic receptors exist, __ and __. Cells of the effector organs may have only one or both types of __ receptors.

The action of catecholamines varies with the type of neuroreceptor stimulated. It should be remembered that catecholamines also are released by the adrenal medulla gland that physiologically and biochemically resembles the sympathetic nervous system. Two types of adrenergic receptors exist, α and β. Cells of the effector organs may have only one or both types of adrenergic receptors.

The __ stage is the emergency reaction that prepares the body to __ or __ from threat. This stage involves the secretion of __ and catecholamines to support physiologic/metabolic activity and boosts the __ system to thwart infection and disease.

The alarm stage is the emergency reaction that prepares the body to fight or flee from threat. This stage involves the secretion of hormones and catecholamines to support physiologic/metabolic activity (Figures 9-2 and 9-3) and boosts the immune system to thwart infection and disease.

general adaptation syndrome The ensuing __ or __ stage requires continued __ of the body's resources to cope and __ a sustained challenge.

The ensuing resistance or adaptation stage requires continued mobilization of the body's resources to cope and overcome a sustained challenge.

general adaptation syndrome The __ stage (currently described as allostatic overload; discussed later) occurs then the body's physiologic and immune systems no longer __ cope with the stressor and marks the onset of __ (diseases of adaptation). That is, when stress continues unabated and __ is not successful, body organs that are __, such as the heart and kidney, may no longer __ and lead to death.

The exhaustion stage (currently described as allostatic overload; discussed later) occurs then the body's physiologic and immune systems no longer effectively cope with the stressor and marks the onset of diseases (diseases of adaptation). That is, when stress continues unabated and adaptation is not successful, body organs that are weak, such as the heart and kidney, may no longer function and lead to death.

The feedback mechanisms of the HPA axis sense and determine the circulating glucocorticoid levels, whereas other tissues passively accept the actions of circulating glucocorticoids. Thus, discrepancy in the glucocorticoid sensing network between the HPA axis and peripheral tissues could possibly produce peripheral tissue __ or __. For example, both high HPA axis reactivity to stress and increased peripheral tissue sensitivity to glucocorticoids are associated with the severity of coronary artery disease

The feedback mechanisms of the HPA axis sense and determine the circulating glucocorticoid levels, whereas other tissues passively accept the actions of circulating glucocorticoids. Thus, discrepancy in the glucocorticoid sensing network between the HPA axis and peripheral tissues could possibly produce peripheral tissue hypercortisolism or hypocortisolism. For example, both high HPA axis reactivity to stress and increased peripheral tissue sensitivity to glucocorticoids are associated with the severity of coronary artery disease

The impact of cortisol on __ development and subsequent risk for future disease also has been investigated. Reynolds offers convincing data associating high maternal cortisol levels during pregnancy with low __ weight. The consequences of cortisol-induced low birth weight have now extended to disease risk in later life, for example, obesity; cardiovascular conditions, such as hypertension; and behavioral disorders attributed to altered brain structure.43-45 Thus, glucocorticoids dramatically affect human pathophysiology and, consequently, __.

The impact of cortisol on fetal development and subsequent risk for future disease also has been investigated. Reynolds offers convincing data associating high maternal cortisol levels during pregnancy with low birth weight. The consequences of cortisol-induced low birth weight have now extended to disease risk in later life, for example, obesity; cardiovascular conditions, such as hypertension; and behavioral disorders attributed to altered brain structure.43-45 Thus, glucocorticoids dramatically affect human pathophysiology and, consequently, longevity.

autonomic nervous system Anatomy of the Parasympathetic Nervous System The parasympathetic nervous system __ and __ energy. The nerve cell bodies of this division are located in the cranial nerve nuclei and in the sacral region of the spinal cord and therefore constitute the __ division. Unlike the sympathetic branch, the preganglionic fibers in the parasympathetic division travel close to the __ they innervate before forming synapses with the relatively short postganglionic neurons

The parasympathetic nervous system conserves and restores energy. The nerve cell bodies of this division are located in the cranial nerve nuclei and in the sacral region of the spinal cord and therefore constitute the craniosacral division. Unlike the sympathetic branch, the preganglionic fibers in the parasympathetic division travel close to the organs they innervate before forming synapses with the relatively short postganglionic neurons

The __ system lacks the generalized and widespread response of the __ system. Specific __ fibers are activated to regulate particular functions. Although the actions of the parasympathetic and sympathetic systems are usually antagonistic, there are exceptions. Peripheral __ resistance, for example, is increased dramatically by __ activation but is not altered appreciably by activity of the __ system. Most blood vessels involved in the control of blood pressure are innervated by __ nerves. To decrease blood pressure, therefore, it is more important to block or paralyze the continuous (tonic) discharge of the __ system than to promote __ activity.

The parasympathetic system lacks the generalized and widespread response of the sympathetic system. Specific parasympathetic fibers are activated to regulate particular functions. Although the actions of the parasympathetic and sympathetic systems are usually antagonistic, there are exceptions. Peripheral vascular resistance, for example, is increased dramatically by sympathetic activation but is not altered appreciably by activity of the parasympathetic system. Most blood vessels involved in the control of blood pressure are innervated by sympathetic nerves. To decrease blood pressure, therefore, it is more important to block or paralyze the continuous (tonic) discharge of the sympathetic system than to promote parasympathetic activity.

The structure and function of the autonomic nervous system (ANS) are complex and still not well understood. Components of the ANS are located in both the __ and the __; however, the ANS is considered to be part of the __ division of the __, even though visceral afferent neurons are certainly an important part of this system. Many neurons of the ANS travel in the spinal nerves and certain cranial nerves.

The structure and function of the autonomic nervous system (ANS) are complex and still not well understood. Components of the ANS are located in both the CNS and the PNS; however, the ANS is considered to be part of the efferent division of the PNS, even though visceral afferent neurons are certainly an important part of this system. Many neurons of the ANS travel in the spinal nerves and certain cranial nerves.

autonomic nervous system The __ nervous system mobilizes energy stores in times of need (e.g., in the "fight or flight" or stress response). The sympathetic division is innervated by cell bodies located from the first __ (__1) through the second __ (__2) regions of the spinal cord and therefore is called the __ division. The __ axons of the sympathetic division form synapses shortly after leaving the spinal cord in the sympathetic (__) ganglia.

The sympathetic nervous system mobilizes energy stores in times of need (e.g., in the "fight or flight" or stress response). The sympathetic division is innervated by cell bodies located from the first thoracic (T1) through the second lumbar (L2) regions of the spinal cord and therefore is called the thoracolumbar division. The preganglionic axons of the sympathetic division form synapses shortly after leaving the spinal cord in the sympathetic (paravertebral) ganglia.

The widespread activity of this system indicates that its components are distributed all over the body. The peripheral autonomic nerves carry mainly __ fibers. The motor component of the ANS is a __-neuron system consisting of __ neurons (__) and __ neurons (__). This arrangement contrasts with the __ nervous system, where a single motor neuron travels from the CNS to the innervated structure. Visceral afferent neurons have their cell bodies in some sensory and cranial ganglia and their fiber processes traveling in peripheral nerves.

The widespread activity of this system indicates that its components are distributed all over the body. The peripheral autonomic nerves carry mainly efferent fibers. The motor component of the ANS is a two-neuron system consisting of preganglionic neurons (myelinated) and postganglionic neurons (unmyelinated). This arrangement contrasts with the somatic nervous system, where a single motor neuron travels from the CNS to the innervated structure. Visceral afferent neurons have their cell bodies in some sensory and cranial ganglia and their fiber processes traveling in peripheral nerves.

The α-adrenergic receptors have been further subdivided according to the action produced. α1- Adrenergic activity is associated mostly with __ or __; α2- adrenergic activity is associated with __ or __. Most of the α- adrenergic receptors on effector organs belong to the α__ class.

The α-adrenergic receptors have been further subdivided according to the action produced. α1- Adrenergic activity is associated mostly with excitation or stimulation; α2- adrenergic activity is associated with relaxation or inhibition. Most of the α- adrenergic receptors on effector organs belong to the α1 class.

The β-adrenergic receptors are classified as β1-adrenergic receptors (which facilitate increased __ rate and contractility and cause the release of __ from the kidney) and β2-adrenergic receptors (which facilitate all remaining effects attributed to β receptors). __ stimulates all α1 and β1 receptors and only certain β2 receptors. The primary response from __, however, is stimulation of the α1-adrenergic receptors that cause __. __ strongly stimulates all four types of receptors and induces general vasodilation because of the predominance of β receptors in muscle vasculatures.

The β-adrenergic receptors are classified as β1-adrenergic receptors (which facilitate increased heart rate and contractility and cause the release of renin from the kidney) and β2-adrenergic receptors (which facilitate all remaining effects attributed to β receptors).11 Norepinephrine stimulates all α1 and β1 receptors and only certain β2 receptors. The primary response from norepinephrine, however, is stimulation of the α1-adrenergic receptors that cause vasoconstriction. Epinephrine strongly stimulates all four types of receptors and induces general vasodilation because of the predominance of β receptors in muscle vasculatures.

autonomic nervous system sympathetic nervous system These preganglionic axons travel several different ways: (1) directly synapsing with __ neurons in the sympathetic chain ganglion at their level; (2) up or down the __ chain ganglion before forming synapses with a higher or lower postganglionic neuron; or (3) through the __ chain ganglion, postganglionic neurons within collateral ganglia

These preganglionic axons travel several different ways: (1) directly synapsing with postganglionic neurons in the sympathetic chain ganglion at their level; (2) up or down the sympathetic chain ganglion before forming synapses with a higher or lower postganglionic neuron; or (3) through the sympathetic chain ganglion, postganglionic neurons within collateral ganglia