The Hypothalamo-neurohypohysial system Flashcards
Describe the embryological origin of the neurones of the posterior pituitary gland
The embryological origin of the neurones is from the neuroepithelial cells of the lining of the third ventricle which develop into nerve cells migrating down towards the optic chiasma and laterally to the paraventricular region close to the third ventricle, forming the supraoptic and paraventricular nuclei respectively.
What separates the anterior and posterior lobe
By an intermediate lobe (the pars intermedia) which in humans is pretty well non-existent, except in pregnant women where there is a limited growth in this region.
Where are the cell bodies present
In the supraoptic and paraventricular nuclei.
What type of neurones mainly terminate in the neurohypophysis and where do they originate from
mainly MAGNOCELLULAR NEURONES
terminate in the NEUROHYPOPHYSIS
They can originate from both the supraoptic and paraventricular nuclei.
What is meant by a magnocellular neurone
Larger than normal neurones
Describe the parvocellular neurones
also some PARVOCELLULAR NEURONES which originate in the PARAVENTRICULAR nuclei terminate either in the median eminence or in other parts of the brain. They are smaller than magnocellular.
What is a consequence of having some parvocellular nuclei terminating in the CNS
Release of central oxytocin and central vasopressin
Describe the role of the supraoptic neurones
Leave hypothalamic supraoptic nuclei Pass through median eminence Terminate in neurohypophysis They are either VASOPRESSINERGIC or OXYTOCINERGIC
Describe the roles of the paraventricular neurones
Originate in paraventricular nuclei Some (parvocellular) VP neurones terminate in median eminence Some (parvocellular) neurones pass to other parts of brain The majority of neurones are magnocellular, and these pass down to the neurohypophysis They are either VASOPRESSINERGIC or OXYTOCINERGIC
Describe the characteristics of magnocellular neurones
They are unmyelinated fibres, and have the distinguishing features of swelling along the axons, particularly near the nerve terminals, called herring bodies. The herring bodies are in close contact with the walls of the capillary network in the neural lobe.
What is the role of herring bodies
They are the site of storage of hormones. Upon the arrival of an action potential the hormones are secreted. Hormones pass into fenestrations of the capillary network and into the general circulation.
Describe the circulation of the posterior pituitary lobe
Arterial blood reaches the posterior lobe capillary network from the inferior hypophysial artery which derives from branches of the posterior communicating and internal carotid arteries. Capillary blood then drains out via the cavernous sinus into the jugular veins.
What is the role of vasopressin in the anterior lobe
It acts as a corticotrophin releasing factor on corticotropic cells. ACTH secreted at optimal levels when Vasopressin and CRH work together
Describe the similarities between vasopressin and oxytocin and what is the consequence of this
Both contain 9 amino acids
Both held by disulphide bonds
They can have similar effects in the body
Describe the differences between vasopressin and oxytocin
Oxytocin- Isoleucine instead of Phenylalanine
Oxytocin- Leucine instead of arginine.
What is the role of the signal peptide in pre-provasopressin
Guides the pre-provasopressin to the Golgi.
Describe the basic steps involved in the synthesis of oxytocin or vasopressin
Pre-prohormone
Prohormone
Hormone- activated version released at the end of the axon
What is pre-provasopressin cleaved into
Vasopressin
93aa neurophysin 2
39 aa glycopeptide
What is the importance of neurophysin
Prevents early degradation by enzymes and diffusion in the herring bodies. Guides hormone to the end of the neurone
How is vasopressin transported down the axon
As pro-vasopressin.
Differences between synthesis of Vasopressin and oxytocin
Same sequence for oxytocin synthesis, except that the neurophysin differs slightly and the glycopeptide is absent- neurophysin 1 in oxytocin
What is meant by a nonapeptide
Differ by two amino acids
Describe V1 receptors
Linked via G proteins to phospholipase C
which acts on membrane phospholipids to produce inositol triphosphate IP3 (and diacyl glycerol, DAG)
which increase cytoplasmic [Ca2+] and other intracellular mediators (PKC)
which produce cellular response
Describe the different types of V1 receptors
V1a:
Arterial/arteriolar smooth muscle (vasoconstriction)
Hepatocytes(glycogenolysis)
CNS neurones (behavioural and other effects)
V1b:
Corticotrophs (ACTH production)
Describe V2 receptors
linked via G proteins to adenyl cyclase
which acts on ATP to form cyclic AMP
which activates protein kinase A
which in turn activates other intracellular mediators
which produce cellular response (aquaporins, AQP2
Describe the different locations of V2 receptors
Collecting duct cells (water reabsorption)
Other effects (endothelial cells, factor VIII and von Willbrandt factor)
What is the principal physiological action of Vasopressin
Principal physiological action is in the renal collecting ducts (principal cells)
where it stimulates water reabsorption
resulting in its ANTIDIURETIC effect
Explain the physiological action of vasopressin in the kidney collecting duct
Vasopressin binds to the V2 receptor on the basolateral (serosal) membrane of the collecting duct cell.
This activates adenyl cyclase which converts ATP into cAMP.
This activates protein kinase A which in turn activates other intracellular mediators including CREB,
Also leads to the synthesis of AQP2.
Aggraphores (vesicles) containing AQP2 are transported to the apical mebrane,
Water moves into tubular fluid by osmotic force.
Synthesis of AQP3 (Vasopressin) and AQP4, which are inserted in the basolateral membrane allow the water to diffuse into the plasma.
Why does water move from lumen-collecting duct-plasma
Kidney has active mechanisms for Na+ reabsorption, water follows movement of Na+
Describe the physiological actions of oxytocin
Major – therapeutic advantage
Uterus
Mammary gland – myoepithelial cells
Minor – unwanted effects
Cardiovascular system
Kidney
Additional physiological
CNS
Describe the basic actions of oxytocin on the uterus during partition
Acts on myometrial cells- contraction - delivery
Describe the basic actions of oxytocin on the breast during lactation
Acts on myoepithelial cells- contraction- milk ejection
Describe the physiological actions of oxytocin on the uterus
UTERUS
Rhythmic contraction; fundus cervix
Increased local prostanoid production
Dilation of cervix
Uterine actions of oxytocin
Suppressed by progesterone
Enhanced by oestrogen
Most marked in late stages of pregnancy
What is the role of prostanoids
Involved in dilation of the cervix
Describe the other physiological actions of Vasopressin
CARDIOVASCULAR - pharmacological
Transient vasodilation & tachycardia
Constriction of umbilical arteries and veins
RENAL - pharmacological
Anti-diuresis and secondary hyponatraemia, i.e. vasopressin-like
CNS – physiological **
Maternal behaviour, social recognition
Explain tend and befriend
Tend : women protect and care for their children
Befriend : women seek out and receive social support
Response to stress- usually seen in females- more stimulated by oestrogen- testosterone acts against it. Fight or flight would not be useful in females- need to look after young
Describe the major clinical uses of oxytocin
INDUCTION OF LABOUR AT TERM
controlled i.v. infusion
PREVENTION TREATMENT OF POST-PARTUM HAEMORRHAGE
Slow i.v. injection/infusion
Local pressor action in uterus suppresses bleeding
FACILITATION OF MILK LET-DOWN
Intranasal spray
AUTISM – SOCIAL RESPONSIVENESS??
Intranasal spray
Why are the constriction effects of oxytocin important
Reduce blood loss- thus reducing the risk of post-partum haemorrhage
Describe the response of vasopressin to increased plasma osmolality
Osmoreceptors located in the anterior hypothalamus are neurones which also have contact with fenestrated capillaries, and hence are in contact with diffusible molecules such as Na+ in the blood. Increased plasma osmolality causes water to leave the osmoreceptors by osmosis. Osmoreceptors shrink, which generates an action potential down an axon which leads to vasopressinergic nuclei in the PVN or SON directly or indirectly. Release of VPP- reabsorption- decreased plasma osmolality.
Some neurones terminate in the brain to stimulate thirst
What else is VPP controlled by
Blood Volume and pressure.
Explain the normal role of baroreceptors and volume receptors on VPP release
In times of high pressure/volume they inhibit the release of VPP.
Explain how a decrease in arterial blood pressure is involved with the release of VPP
Baroreceptors have a lower firing rate.
Reduced inhibition of VPP release
Axons sent to hypothalamus- less inhibition of vasopressinergic neurones- release of VPP
What normally stimulates VPP release in terms of decreased blood pressure
Extreme factors, such as haemorrhage or dehydration.
What influences from higher centres can stimulate VPP release
Stress.
Describe the neuroendocrine arc involved in the release of oxytocin
Sucking of breast
Stimulates Neural Afferent Limb
Stimulates neurones in the hypothalamus to stimulate the release of oxytocin- endocrine efferent limb
Milk ejection
How can we treat a lack of oxytocin
parturition and milk ejection effects induced/replaced by other means
What does a lack of VPP lead to
Diabetes Insipidus
Symptoms of diabetes insipidus
Polydipsia (increased thirst)
Polyuria (large volumes of urine)
Urine very dilute (hypo-osmolar)
What are the two different causes of diabetes insipidus
NEPHROGENIC
End-organ (kidneys) resistance to vasopressin
CENTRAL (or CRANIAL)
Absence or lack of circulating vasopressin
Describe the consequences of too much VPP due to a tumour
NB – Syndrome of inappropriate ADH = too much vasopressin
Describe baroreceptor reflex
Increased BP- autonomic nervous system stimulated, VPP inhibited.
Stimulation of parasympathetic activity, inhibition of sympathetic activity.
Where are low pressure baroreceptors found
Right atrium
Certain large systemic veins (vena cava, hepatic veins).
Respond to changes in venous volume
Where are high pressure baroreceptors found
Stretch-sensitive nerve endings located in the walls of the carotid sinus and aortic arch- axons pass up carotid sinus and vagus nerves to the brainstem. from which other neurones innervate the cardiovascular centre and the hypothalamus, including the vasopressinergic neurones.
How is BP calculates
Stroke volume x Total Peripheral Resistance (resistance increases in narrower arteries)
