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68 Cards in this Set
- Front
- Back
Disease: Syndrome of Inappropriate Antidiuretic Hormone Hypersecretion (SIADH) |
Rare form of hyperfunction of the PP, producing excessive level of vasopressin (VP) that is inappropriate for plasma osmolarity in individual |
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What causes an individual to develop Syndrome of Inappropriate Antidiuretic Hormone Hypersecretion (SIADH)? |
most likely not actually a pituitary problem - often caused by ectopic (in an abnormal place or position) source of VP (e.g. lung cancer) can occur after AP pituitary surgery (Initial diabetes insipidus (low VP) is followed by SIADH (high VP) which shouldbe managed with reduced fluid intake to prevent hyponatremia |
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Syndrome of Inappropriate Antidiuretic Hormone Hypersecretion (SIADH) Effects on kidney, urine, and plasma? |
Water reabsorption by kidney is increased and leads to a reduced renal volume and more concentrated urine consequence is hyponatremia (decrease in plasma sodium concentration) |
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Diabetes Insipidus (DI) |
failure of the posterior pituitary to produce vasopressin (VP, ADH) presents as a polyuria (excess urine) and polydipsia (consequential excess drinking), so it's important to rule out diabetes mellitus |
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What can cause diabetes insipidus? |
- Post-pituitary surgery that has caused some form of damage to the posteriorlobe -Metastases and posterior lobe failure -Fractures of the skull -End-organ kidney failure -Transient after transphenoidal pituitary surgery |
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How is diabetes insipidus diagnosed? |
fluid/water deprivation test with hourly measurements of urine volume and osmolarity (Monitor for dehydration due to large water volume loss) |
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What is the treatment for DI? |
Use of a VP analogue (that contains a D- rather than an L- form of arginine in themolecule) to provide a longer half life than VP |
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Oxytocin deficiency |
only a problem in breast feeding patients and these individuals can be given oxytocin analogues |
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Oxytocin excess |
Excess production of oxytocin (e.g. ectopic tumor) is rarely seen as it won’t produce symptoms |
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Nonapeptides are transported to their target tissues by which 3 mechanisms? |
1. Release of hormones into the blood occurs either via the general circulation fromthe PP or into the hypothalamic-hypophysial portal system (and AP) 2. Release at nerve endings across synapses within the CNS where the nonapeptidescan act as neurotransmitters 3. Release from dendrites terminating at the 3rd ventricle which can carry the hormones into the CSF for transport to central receptors |
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In the blood, how are neurohormones transported? What is their half life? |
In the blood neurohormones are transported to target tissues “unbound” witha half life of around 5 min |
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What type of receptors are VP receptors? How many forms do they exist in? |
All VP receptors are 7-pass transmembrane G-protein coupled receptors Exist in at least 3 forms, known as V1a, V1b (also called V3), and V2 |
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V1a, V1b (V3) and V2 are found on which chromosomes? What is the percentage of sequence homology between the three? |
V1a (on chr 12), V1b/V3 (on chr 1) and V2 (on chr X) have 45% sequence homology |
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What is true of the binding between Vasopressin, VTR, Oxytocin, and OTR? |
Vasopressin can bind OTR but oxytocin cannot bind VTR |
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Vasopressin and oxytocin are ______, differing by only two amino acids in the ring and side branches. |
nonapeptides |
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The genes for vasopressin and oxytocin are located on chromosome ___. |
chromosome 20 |
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vasopressin and oxytocin are first produced as pre-hormones which are then processed in the _____. |
ER |
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Pro-vasopressin becomes _______ + _______ + ______. |
vasopressin + neurophysiology II + copeptin (GP) |
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Vasopressin target tissues: V1a receptors are present on which target tissues? |
vascular smooth muscle, hepatocytes, cardiomyocytes, platelets, adrenal cortex, kidneys, CNS (hippocampus, cortex, thalamus, cerebellum) |
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Vasopressin target tissues: Vlb/V3 receptors are found on which target tissues? |
AP corticotrophin, heart, lungs, thymus, mammary glands and CNS (hippocampus, cortex, thalamus, cerebellum) |
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Vasopressin target tissues: V2 receptors are found on which target tissues? |
Renal cortical and medullary collecting ducts and Loops of Henle, vascular endothelial cells |
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V1a/b receptor signaling pathways: ______ is a co-transcriptional element that activates a transcription factor, ____ (at active sites). Transcription of different genes occurs via the ________--______-____ complex. |
CREB-BP, CREB (cAMP response element-binding protein) CREB--CREB-BP complex |
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V2 receptor and its signaling pathway: A key molecule influenced by vasopressin through the V2 receptor is ______. |
aquaporin |
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What is the role of aquaporin (influenced by vasopressin through the V2 receptor pathway)? |
acts as a transmembrane protein to transport water molecules via an osmotic gradient |
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What is the role of the vasopressin-dependent aquaporin (AQP2)? |
facilitates movement of water from tubular fluid into cells |
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How is the movement (via aggraphores) and synthesis of AQP2 vasopressin-dependent? |
- AQP2 sequestered in aggraphores is transported to the apical membrane viamicrotubules and microfilaments influenced by VP - After insertion and use, the receptor protein is inactivated/returned to themembrane for reuse, a process that is fine tuned by VP |
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Describe the basic intracellular mechanism between VP and AQP in the collecting duct. |
1. Vasopressin (VP) binds to its V2 receptor 2. This activates the associated G-protein 3. G protein activates adenyl cyclase (AC) enzyme 4. AC induces formation of cAMP 5. cAMP activates (phosphorylates) protein kinase A (PKA) |
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Review: what are the three mechanisms by which Vasopressin can act? (via which type of neurons? acting as what type of molecule? target?) |
1. via parvocellular neurons, acting as a neurotransmitter, to CNS 2. via parvocellular neurons, acting as neurohormone, to (walls of plexus in) median eminence 3. via magnocellular neurones (terminate in NP), acting as neurohormone, to general circulation |
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Physiological actions of VP in CNS? |
behavioral and other effects |
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Physiological actions of VP secreted to median eminence? |
Corticotrophin (ACTH) release (AP) |
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Physiological actions of VP secreted into general circulation? |
1. renal water reabsorption 2. vasoconstriction 3. vasodilation 4. Factor VIII and von Willebrand factor 5. Hepatic glycogenolysis |
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Physiology related to where the VP receptors are. V1a receptors are linked to which principle actions of VP? |
vasoconstriction, CNS effects, hepatic glycogenolysis, platelet aggregation |
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Physiology related to where the VP receptors are. V1b (V3) receptors are linked to which principle actions of VP? |
corticotrophin release, CNS effects |
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Physiology related to where the VP receptors are. V2 receptors are linked to which principle actions of VP? |
renal water absorption, factor VIII and von Willebrand synthesis (VP used to stimulate VIII in hemophilia), vasodilation |
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Both V1a and V1b (V3) receptors are linked to which principle action(s) of VP? |
CNS effects |
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What are the peripheral actions of VP? |
-as an antidiuretic (principally water reabsorption in collecting duct) -maintenance of renal countercurrent multiplier system -as a vasoconstrictor -as a vasodilator
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Describe the peripheral action of VP acting as an antidiuretic. |
- Migration of aggraphores and insertion AQP2 into AM for waterreabsorption - Activation of CREB and AQP2 gene expression - Degradation /recycling of V2 receptor via β arrestin activation - Recycling of AQP2 - Synthesis of AQP3 to facilitate water leaving via BLM |
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Describe the peripheral actions of VP and maintenance of the renal countercurrent multipliersystem. |
Maintenance of high medullary interstitial concentrations of solute needed forwater reabsorption and urine concentration |
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If vasopressin is administered and _______ is blocked with an antagonist,vasoconstriction can be blocked. |
V1R |
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If vasopressin is administered and V1R activity is blocked with an antagonist,vasoconstriction can be blocked. Kidney-independent (i.e. directly on vasculature) vasodilation occurs,decreasing peripheral _______ and resulting in a ______ in BP. This is due to_____-mediated effect involving local release of vasodilator ______, which acts onadjacent smooth muscle to cause relaxation and dilation. |
resistance, decrease V2R-mediated, NO (Summary: vasopressin administered, V1R activity blocked in, V2R mediates release of vasodilator NO, vasodilation occurs, decrease in BP) |
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Describe the adenohypophysial action of VP |
VP (often in conjunction with CRH) released into the hypothalamo-AP portal system is directed to the V1b (V3) receptors in the corticotrophs where it isstimulatory - Corticotrophin (ACTH) release potentiates effects of CRH - ACTH also stimulates cortisol production; cortisol has an indirect negativefeedback on CRH |
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In long term stress, VP drives production of ______ and is associatedwith increased levels of circulating _______ and enhanced negative feedback on______ release |
ACTH, cortisol, CRH |
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What is the central action of VP? |
Vasopressin is released from dendrites abutting walls of 3rd ventricle and acts as a neurohormone |
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How does VP in CSF compare to CP in plasma? |
VP in CSF is higher than in plasma |
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In CSF, VP is transported to parts of the brain where its action is mediated by what type of receptors? |
V1aR or V1bR |
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What type of effects does VP have when it acts as a neurohormone and takes central action? |
Behavioral effects |
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Male prairie vole monogamy and aggression, and females with newlitters, is correlated with _____ in brain |
V1aR |
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In humans, autism is associated with decreased social functioning and apolymorphism in the ___ receptor gene |
VP |
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_______ VP action is associated with drinking, learning andmemory functions (via VP in CSF or through neuron projections) |
Central |
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What is the most important factor of the control of VP secretion? |
degree of hydration, via osmoreceptors (normal physiology), baroreceptors (less sensitive; operates when blood volume is markedly decreased e.g. hemorrhage), or in response to stressors |
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VP acts via ______ when there's no change in osmolarity. |
baraoreceptors |
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When there's an increase in plasma osmolality, VP neurons increase in firing rate and act via _____. |
osmoreceptors |
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Osmoreceptors are present in osmosensitive (stretch-responsive) cells in _______, and vasopressinergic neurons in _______. |
circulation, hypothalamus |
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Osmoreceptors lie outside the ____________ in subfornical organ (SFO) and organum vasculosum (OVLT) and can directly contact diffusible solutes (e.g Na+ in blood) Regulates thirst (influences drinking) through _____, which also regulates VP secretion. |
blood brain barrier, AII, |
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Vasopressinergic neurons fire more regularly when osmolarity of surrounding medium is (increased/decreased). |
Increased |
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What do osmoreceptors detect? |
osmoreceptors detect increases in plasma osmolarity associated with VP increase |
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Where are baroreceptors present? |
in high pressure (arteries) and low pressure (veins) parts of circulation |
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Where are baroreceptors present in high pressure parts of circulation (arteries)? |
walls of carotid sinus and vagus nerves |
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Where are baroreceptors present in low pressure parts of circulation (veins)? What do they respond to? |
located in right atrium, vena cava and hepatic veins and respond to changes in venous blood volume |
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What type of baroreceptor responses lead to brain stem and then on cardiovascular center and to vasopressinergic neurons in hypothalamus? |
both high pressure and low pressure responses |
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When stimulated (e.g. increase in BP or volume) baroreceptors inhibit both ____ and ____ release (baroreceptor reflex) while also increasing PSN activity. |
SNS, VP |
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How is the baroreceptor reflect regulated? |
sympathetic and parasympathetic regulation |
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How can the stimulation of baroreceptors, due to an increase in mean arterial pressure, lead to a decrease in BP? (Baroreceptor reflex) |
stimulation of baroreceptors --> VP decrease --> decrease in water reabsorption via collecting ducts --> decrease in vasoconstriction and blood pressure |
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Posterior pituitary production of Oxytocin (OT) Receptors and mechanisms of action? |
GPCR via PLC activation Locus is on Chr 3 producing a 389 AA sequence |
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Posterior pituitary production of Oxytocin (OT) Physiological effects? |
- Peripheral and central effects including social and maternal behaviors - OT produced by magnocellular neurons of male (stimulation of ejaculation and increase A by Leydig cells) and female (pregnancy and lactation) equally -uterine contraction, milk ejection reflect, OT central effects |
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Posterior pituitary production of Oxytocin (OT) Effects on uterine contraction |
- Prior to labor onset, uterus is dominated by progesterone and OTR is unexpressed - Distension of uterus (mechanoreceptors in wall) leads to estrogen increase and OTR are synthesized - Stretch sends impulses up afferent nerves in inferior hypogastric plexus to hypothalamus and OT is released - OT is also synthesized locally in the uterus as well as ovary, testis, heart and pancreas |
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Posterior pituitary production of Oxytocin (OT) Effects on the Milk Ejection Reflex |
- Post-partum suckling by baby leads to OT release from PP - Influenced by estrogens, progesterone, iodothyronines and prolactin, myoepithelial cells in mammary ducts express OTR and contract - Milk is ejected from nipple to baby’s mouth - Milk ejection reflex is controlled by positive feedback |
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Posterior pituitary production of Oxytocin (OT) Oxytocin (OT) Central effects- released by dendrites into the third ventricle (where in the brain can OTR be found? What is OT associated with in females?) |
- OTR can be found in various parts of the brain - In females, OT is associated with: ▫ various behavioral effects in mothers e.g maternal bonding andprotectiveness ▫ OT-dependent appeasing and less aggressiveness ▫ attenuation of responses such as fear (decreases glucocorticoid production) and positive stimulation of trust and generosity |