Homeostasis and The Stress Response
HomeostasisDefinition: The tendency of an organism or a cell to regulate its internal conditions, usually by a system of feedback controls, so as to stabilize health and functioning, regardless of the outside changing conditions. http://www.biology-online.org/dictionary/Homeostasis
Influences that tend to deregulate internal conditions are termed stressorsThis is a different definition than we are used to hearingStressors can be physical, emotional, environmental, etc.
Compensatory mechanisms to counteract the effect(s) of stressors involve Autonomic nervous systemAdrenal cortexRenin-angiotensin-aldosterone system (RAAS)Many others.*
Three Components to Physiologic Stress Response*
Three Components to Physiologic Stress Response*
Neuroendocrine Pathways and Physiologic Responses to StressDescription*
Neuroendrocrine Pathways and Physiologic Responses to StressDescriptionShows the different responses to stressorsMay perceive stressor in the cerebral cortex or the stressor may be unconsciousActivating the RAS (the part of the brain that keeps up awake) leads to increased muscle tension and alertnessLimbic system produces the emotional responseThe locus ceruleus activates the ANS (sympathetic nervous system), which activates the adrenal medulla and the activation of the RAAS
Neuroendrocrine Pathways and Physiologic Responses to StressDiagram*
Neuroendrocrine Pathways and Physiologic Responses to Stress
*Adapted from Porth, 2011, Essentials of Pathophysiology,3rd ed., Lippincott, p. 213(CorticotropinReleasing Factor)(AdrenocorticotropicHormone)Activation of the RAAS
Activation of the Sympathetic Nervous System (SNS)*
Activation of the Sympathetic Nervous System (SNS)
Heart rate Blood pressureCool skinAll of the blood is being shunted away form the skin to the skeletal muscleDiaphoresis to keep body coolPupil dilation Blood glucose to have fuel for muscle Peristalsis Urine outputDo not want to devote metabolic energy to urine formation*
Release of Norepinephrine
*NorepinephrineVasoconstrictionof arteries and veins(Venous return to the heart/CO and Blood Pressure)Pupil Dilation 1 21Heart rateContractilityRelease of reninAll of these increase blood pressure1Release of Norepinephrine
Epinephrine Released byAdrenal Medulla
*EpinephrineVasoconstrictionBlood pressureVenous return/COPupil dilation 1Heart rateContractility Release of renin11 2Dilation of skeletal muscle vascular beds and bronchi2Epinephrine Released byAdrenal Medulla
Activates alpha 1 and alpha 2 as well as beta 2 receptors
Role of Epinephrine on B2 Receptors*
*EpinephrineDegradation of cholesterol to bile SaltsFree fatty acids that canbe used for ATP synthesis- maximizes energy productionCholesterol to be available for the repair of cell membranesLipolysis of triglycerides22
*EpinephrineLiverSkeletal MuscleGluconeogenesisGlycogen Breakdown Blood Glucose2 2 Protein breakdown/amino acid release
Norepinephrine stimulates beta-1 receptors to cause*
Norepinephrine stimulates beta-1 receptors to cause:Lipolysis of triglyerides beta 2Vasoconstriction of blood vessels - alphaDecreased heart rate muscarinic receptorsRenin release*
Release of Renin and ADH (Antidiuretic Hormone)*
Release of Renin and ADH (Antidiuretic Hormone)Renin is released in response to SNS stimulation of beta-1 receptors in the kidneyRelease of renin initiates renin-angiotensin-aldosterone system (RAAS)Angiotensin II causes vasoconstriction leading to Blood pressureAldosterone causes increased reabsorption of water in the kidneys causing venous return cardiac outputAldosterone has a steroid structure, like cortisol, and is referred to as a mineralocorticoid.-----------------------------------------------------------------------ADH (antidiuretic hormone) is released from the posterior pituitary in response to SNS stimulationADH causes increased reabsorption of water in the kidneys causing venous return cardiac output*
ReninAngiotensinAldosterone System (RAAS)Diagram*
ReninAngiotensinAldosterone System (RAAS)Diagram*Must know this!!!Porth, 2011, Essentials of Pathophysiology, 3rd ed., Lippincott, p. 420.
Hypothalamus-Anterior Pituitary FunctionDiagram*
Hypothalamus-Anterior Pituitary Function*Porth, 2007, Essential of Pathophysiology, 2nd ed., Lippincott, p. 666
Hypothalamus-Anterior Pituitary FunctionDescription*
Hypothalamus-Anterior Pituitary FunctionDescriptionThe hypothalamus and the anterior pituitary are important in the stress response
Cells release releasing factors that travel through the vessels and cause cells in the anterior pituitary to release tropic hormonesGo to target glands to release peripheral hormonesThe hormone has a negative feedback on the anterior pituitary and the hypothalamus to decrease the hormone
*Feedback InhibitionDiagramPorth, Essentials of Pathophysiology, 3rd ed., 2011, Lippincott, p.770.
Peripheral Glands Controlled by the PituitaryDiagram*
Peripheral Glands Controlled by the Pituitary*Porth, 2011, Essential of Pathophysiology, 3rd ed., Lippincott, p. 770
Regulation of Cortisol Synthesis and SecretionDescription*
Regulation of Cortisol Synthesis and SecretionDescriptionAdrenals do not store glucocorticoidsAmount released = amount madeRegulated by negative feedback loopCircadian rhythm bedtime, sleep, peak on awakening, during dayStress increases CRH synthesis and release.Some of the inputs into the hypothalamus include stress and circadian rhythmsAlso regulated by negative feedback from cortisol in the peripheryAlso acts on cells in the anterior pituitaryACTH circulates all over the body, such as the adrenal cortexBiological effects of cortisol are on nearly every body cellCortisol secretion is low at night, at its highest in the morning
Regulation of Cortisol Synthesis and SecretionDiagram*
Regulation of Cortisol Synthesis and Secretion*Lehne, 2009, Pharmacology for Nursing Care, 7th ed., Elsevier, p. 711
Diurnal Secretion of CortisolDiagram*
Diurnal Secretion of Cortisol*When we administer corticosteroids pharmacologically, we try to mimic this diurnal rhythm.Stewart, Paul, 2003, The adrenal cortex in Larson, et al, eds., Williams Textbook of Endocrinology, Saunders.
CortisolPhysiologic EffectsCarbohydrate metabolismFat metabolismProtein metabolismCardiovascularCentral nervous systemStress *
CortisolCarbohydrate MetabolismCarbohydrate MetabolismGluconeogenesis the synthesis of new glucose molecules in the liverPeripheral glucose utilization in the peripheryIncreased gluconeogenesis and decreased peripheral glucose utilization will increase glucose levels in the body glucose uptake muscle/adipose tissuePromote glucose storage (glycogen)
All these make glucose more available to the brain!*
GlucocortsSupplying the brain with glucose is essential for survival.
Glucocorts help meet this need with CHO metabolism thru the following 4 ways. All 4 actions increase glucose availablility during fasting and thereby ensure the brain will not be deprived of its primary source of energy.
When present in chronically high levels for a prolonged period of time, glucocorts produce symptoms much like those of diabetics.
Pro metab: promote pro breakdown. If present at high levels for prolonged pd of time, glucorts will cause a thinning of skin, muscle wasting, and negative nitrogen balance
Fat metab: glucocorts promote lipolysis (fat breakdown). When present at high levels for an extended time, glucocorts cause fat redistribution, given the pt a potbelly, moon face, and buffalo hump on the back. *
CortisolProtein MetabolismPromote catabolism
Amino acids provide substrate for hepatic gluconeogenesis*
CortisolFat MetabolismPromote lipolysisIncreases the amount of energy that is available to the cells
Free fatty acids provide substrate for the Krebs cycle.
CortisolCardiovascular SystemRequired for the integrity of the blood vessels, including their ability to constrict
CortisolCentral Nervous System*
CortisolCentral Nervous SystemIncreases excitation
CortisolStress ResponseStress:Stress increases CRH secretion by the hypothalamusCRH secretion stimulates ACTH (adrenocorticotropic hormone) secretion, which increases cortisol secretion*
Effect of Acute Stress*
Effect of Acute StressGoals: survival, vigilance, alertness, arousal, aggression
Designed to be self-limiting and short term
Similar to the Fight or flight SNS activation shortest term
Activation of the HPA (hypothalamus pituitary adrenal) axis promotes energy utilization and availability of substrate for tissue repair. longer term.Even though this is longer term, it is not designed to be continually activated*