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Endocrinology > The Hypothalamo-neurohypohysial system > Flashcards

The Hypothalamo-neurohypohysial system Flashcards

1
Q

Describe the embryological origin of the neurones of the posterior pituitary gland

A

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.

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2
Q

What separates the anterior and posterior lobe

A

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.

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3
Q

Where are the cell bodies present

A

In the supraoptic and paraventricular nuclei.

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4
Q

What type of neurones mainly terminate in the neurohypophysis and where do they originate from

A

mainly MAGNOCELLULAR NEURONES
terminate in the NEUROHYPOPHYSIS
They can originate from both the supraoptic and paraventricular nuclei.

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5
Q

What is meant by a magnocellular neurone

A

Larger than normal neurones

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6
Q

Describe the parvocellular neurones

A

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.

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7
Q

What is a consequence of having some parvocellular nuclei terminating in the CNS

A

Release of central oxytocin and central vasopressin

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8
Q

Describe the role of the supraoptic neurones

A 
Leave hypothalamic
supraoptic nuclei
Pass through
median eminence
Terminate in 
neurohypophysis
They are either 
VASOPRESSINERGIC or OXYTOCINERGIC
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9
Q

Describe the roles of the paraventricular neurones

A 
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
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10
Q

Describe the characteristics of magnocellular neurones

A

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.

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11
Q

What is the role of herring bodies

A

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.

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12
Q

Describe the circulation of the posterior pituitary lobe

A

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.

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13
Q

What is the role of vasopressin in the anterior lobe

A

It acts as a corticotrophin releasing factor on corticotropic cells. ACTH secreted at optimal levels when Vasopressin and CRH work together

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14
Q

Describe the similarities between vasopressin and oxytocin and what is the consequence of this

A

Both contain 9 amino acids
Both held by disulphide bonds
They can have similar effects in the body

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15
Q

Describe the differences between vasopressin and oxytocin

A

Oxytocin- Isoleucine instead of Phenylalanine

Oxytocin- Leucine instead of arginine.

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16
Q

What is the role of the signal peptide in pre-provasopressin

A

Guides the pre-provasopressin to the Golgi.

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17
Q

Describe the basic steps involved in the synthesis of oxytocin or vasopressin

A

Pre-prohormone
Prohormone
Hormone- activated version released at the end of the axon

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18
Q

What is pre-provasopressin cleaved into

A

Vasopressin
93aa neurophysin 2
39 aa glycopeptide

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19
Q

What is the importance of neurophysin

A

Prevents early degradation by enzymes and diffusion in the herring bodies. Guides hormone to the end of the neurone

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20
Q

How is vasopressin transported down the axon

A

As pro-vasopressin.

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21
Q

Differences between synthesis of Vasopressin and oxytocin

A

Same sequence for oxytocin synthesis, except that the neurophysin differs slightly and the glycopeptide is absent- neurophysin 1 in oxytocin

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22
Q

What is meant by a nonapeptide

A

Differ by two amino acids

23
Q

Describe V1 receptors

A

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

24
Q

Describe the different types of V1 receptors

A

V1a:
Arterial/arteriolar smooth muscle (vasoconstriction)

Hepatocytes(glycogenolysis)

CNS neurones (behavioural and other effects)

V1b:
Corticotrophs (ACTH production)

25
Q

Describe V2 receptors

A

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

26
Q

Describe the different locations of V2 receptors

A

Collecting duct cells (water reabsorption)

Other effects (endothelial cells, factor VIII and von Willbrandt factor)

27
Q

What is the principal physiological action of Vasopressin

A

Principal physiological action is in the renal collecting ducts (principal cells)
where it stimulates water reabsorption
resulting in its ANTIDIURETIC effect

28
Q

Explain the physiological action of vasopressin in the kidney collecting duct

A

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.

29
Q

Why does water move from lumen-collecting duct-plasma

A

Kidney has active mechanisms for Na+ reabsorption, water follows movement of Na+

30
Q

Describe the physiological actions of oxytocin

A

Major – therapeutic advantage
Uterus
Mammary gland – myoepithelial cells

Minor – unwanted effects
Cardiovascular system
Kidney

Additional physiological
CNS

31
Q

Describe the basic actions of oxytocin on the uterus during partition

A

Acts on myometrial cells- contraction - delivery

32
Q

Describe the basic actions of oxytocin on the breast during lactation

A

Acts on myoepithelial cells- contraction- milk ejection

33
Q

Describe the physiological actions of oxytocin on the uterus

A

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

34
Q

What is the role of prostanoids

A

Involved in dilation of the cervix

35
Q

Describe the other physiological actions of Vasopressin

A

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

36
Q

Explain tend and befriend

A

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

37
Q

Describe the major clinical uses of oxytocin

A

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

38
Q

Why are the constriction effects of oxytocin important

A

Reduce blood loss- thus reducing the risk of post-partum haemorrhage

39
Q

Describe the response of vasopressin to increased plasma osmolality

A

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

40
Q

What else is VPP controlled by

A

Blood Volume and pressure.

41
Q

Explain the normal role of baroreceptors and volume receptors on VPP release

A

In times of high pressure/volume they inhibit the release of VPP.

42
Q

Explain how a decrease in arterial blood pressure is involved with the release of VPP

A

Baroreceptors have a lower firing rate.
Reduced inhibition of VPP release
Axons sent to hypothalamus- less inhibition of vasopressinergic neurones- release of VPP

43
Q

What normally stimulates VPP release in terms of decreased blood pressure

A

Extreme factors, such as haemorrhage or dehydration.

44
Q

What influences from higher centres can stimulate VPP release

A

Stress.

45
Q

Describe the neuroendocrine arc involved in the release of oxytocin

A

Sucking of breast
Stimulates Neural Afferent Limb
Stimulates neurones in the hypothalamus to stimulate the release of oxytocin- endocrine efferent limb
Milk ejection

46
Q

How can we treat a lack of oxytocin

A

parturition and milk ejection effects induced/replaced by other means

47
Q

What does a lack of VPP lead to

A

Diabetes Insipidus

48
Q

Symptoms of diabetes insipidus

A

Polydipsia (increased thirst)

Polyuria (large volumes of urine)

Urine very dilute (hypo-osmolar)

49
Q

What are the two different causes of diabetes insipidus

A

NEPHROGENIC
End-organ (kidneys) resistance to vasopressin

CENTRAL (or CRANIAL)
Absence or lack of circulating vasopressin

50
Q

Describe the consequences of too much VPP due to a tumour

A

NB – Syndrome of inappropriate ADH = too much vasopressin

51
Q

Describe baroreceptor reflex

A

Increased BP- autonomic nervous system stimulated, VPP inhibited.
Stimulation of parasympathetic activity, inhibition of sympathetic activity.

52
Q

Where are low pressure baroreceptors found

A

Right atrium
Certain large systemic veins (vena cava, hepatic veins).
Respond to changes in venous volume

53
Q

Where are high pressure baroreceptors found

A

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.

54
Q

How is BP calculates

A

Stroke volume x Total Peripheral Resistance (resistance increases in narrower arteries)

Endocrinology (11 decks)

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