Neurohypophysial Disorders Flashcards by Wasim Silmi

Which neurons that originate in the hypothalamus project to the neurohypophysis

PVN and supraoptic nucleus

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What are the neurohypophysis hormones

Oxytocin and VP

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Where are oxytocin and vasopressin originally synthesised

In the hypothalamus

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Difference in posterior pituitary and anterior in pituitary MRI?

Bright spot in the neurohypophysis

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Where does VP act

collecting duct cells

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What receptor does VP stimulate

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What does VP cause to happen to a collecting duct cell

Stimulates synthesis and assembly of aquaporin 2 at the luminal/apical membrane.

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Overall effect of VP? And on urine?

Increased water transport

Concentrates urine

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Other non-diuresis linked effects of VP? What receptors (3)

Vasoconstrictor Activity -‐ V1a
Corticotrophin (ACTH) Release -‐ V1b
Releases Factor VIII and von Willebrand Factor -‐ V2

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Vasopressin - osmoreceptors within the BBB are sensitive to the C/D of plasma and have neurons the project into the hypothalamic paraventricular nucleus and supraoptic nucleus to stimulate VP release

BBB = circumventricular organum vasculosom 
C/D = concentrations/osmolality

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How do osmoreceptors detect osmolality

High osmolality -> Osmoreceptors detect this as water will flow out of it due to the concentration gradient and the osmoreceptor shrink

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What happens when an osmoreceptor shrinks to its firing rate

As it shrinks it neuronal firing increases

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Oxytocin causes constriction of X at Y

myometrium at parturition

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2 forms of Diabetes Insipidus

CENTRAL (or CRANIAL)

NEPHROGENIC

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What is the problem in CENTRAL (or CRANIAL) diabetes Insipidus

Absence or lack of circulating vasopressin, neurohypophysis does not make enough vasopressin/ADH.

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What is the problem in NEPHROGENIC diabetes Insipidus

End‐organ (kidneys) resistance to vasopressin. Less common.

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Which form of diabetes insipidus is more common

Central/cranial

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What causes acquired DI? (6)

Damage to neurohypophysial system through:
• Traumatic brain injury to neurohypophysis
• Pituitary surgery
• Cerebral thrombosis
• Tumours (intrasellar and suprasellar, craniopharyngioma)
• Metastasis to the pituitary gland (e.g. through breast cancer).
• Granulomatous infiltration of median eminence (e.g. TB and sarcoidosis

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can you get congenital DI?

Yes

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What causes Nephrogenic Diabetes Insipidus (2)

Congenital mutation in gene for V2 receptor or AQP2 water channel
Or acquire through through drugs (e.g. lithium which is used for BPD).

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What drug for what disorder can cause DI

Lithium which is used for BPD

Signs and symptoms of DI? (5)

Large volumes of urine (polyuria)
Very dilute urine (hypo-osmolar)
Nocturia
Thirst and increased drinking (polydipsia)
Dehydration (and consequences like death) if fluid intake is not maintained
Possible disruption of sleep with associated problems
Possible electrolyte imbalance

How does DI cause thirst?

lack vasopressin -> can’t reabsorb water -> increase in urine excretion volume -> hypotonic urine and a reduction in extracellular fluid volume
This leads to an increase in plasma osmolarity (and sodium) so that will lead to osmoreceptors triggering vasopressin release and it will trigger thirst (polydipsia).

Why might a patient with DI have a normal plasma osmolarity

They are well hydrated

What is polydipsia

Thirst excessively

What is psychogenic polydipsia

increased drive to drink by psychiatric patients

What population is psychogenic polydipsia frequently seen in and why

Frequently seen in psychiatric patients, anti-cholinergic medications can cause a dry mouth

Difference between psychogenic polydipsia and DI?

Ability to secrete VP is not impaired

``` Results of a normal hydrated urine osmolarity test in: Normal people Psychogenic polydipsia Nephrogenic DI Central DI ```

All normal between 290-270mOsm/kg H2O

Normal range of urine osmolarity?

290-270mOsm/kg H2O

``` Results of a fluid deprived urine osmolarity test in: Normal people Psychogenic polydipsia Nephrogenic DI Central DI ```

Normal people will have high urine osmolarity as they will release AVP (arginine vasopressin) and concentrate the urine to preserve plasma osmolarity In psychogenic polydipsia, the vasopressin system is working fine as so will have almost the same but justt slightly lower With central and nephrogenic diabetes insidus they have no/little change

``` Results of a DDAVP administered urine osmolarity test in: Normal people Psychogenic polydipsia Nephrogenic DI Central DI ```

You are giving extra vasopressin so this will concentrate the urine of a normal person and the person with polydipsia The person with CENTRAL diabetes insipidus will also be able to concentrate their urine because their vasopressin receptors are working fine and can be stimulated by DDAVP The NEPHROGENIC diabetes insipidus patient will not respond because they have vasopressin anyway it just doesn't have any effect

Biochemical features of DI?

Hypernatremia Raised urea levels Increased plasma osmolality. Dilute (hypo-osmolar) urine

What is the problem with using biochemical markers to test for DI? which biochemical marker is immune to this?

may be hidden if the patient is drinking a shit tonne of water Dilute (hypo-osmolar) urine will always be hyperosmolar in DI

Treatment for central DI?

Desmopressin (DDAVP)

Which receptor are you trying to stimulate with argipressin? which is stimulated unwantlingly?

V2 in kidney V1 in VSMC and NVSMC, pituitary, liver, platelets will however all be stimulated to

What drug stimulates only V2 receptors

Desmopressin (DDAVP)

Desmopressin (DDAVP) stimulates ...

V2 receptors

RoA for DDAVP?

nasally, orally, subcutaneous injection

What should you tell a patient to do after giving them DDAVP?

Not drink as much water

Treatment for nephrogenic DI?

Thiazide Diuretics

What is The Syndrome of Inappropriate ADH (SIADH)

The plasma vasopressin concentration is INAPPROPRIATE for the existing plasma osmolarity

Too much ADH secretion is known as...

The Syndrome of Inappropriate ADH (SIADH)

What does The Syndrome of Inappropriate ADH (SIADH) cause

hyponatraemia | euvolaemia

How does excess VP cause hyponatremia and euvolaemia (mention ANP)

Increased VP Increased H20 reabsorption from renal collecting ducts Expansion of ECF volume ( Hyponatremia directly caused) Atrial natriuretic peptide (ANP) released from right atrium in response to increased ECF volume which causes Natriuresis (loss of sodium in urine)  Loss of water along with sodium Euvolaemia AND hyponatremia

3 signs of SIADH

Raised urine osmolarity Decreased urine volume (initially) HYPONATRAEMIA -‐ decrease in plasma sodium concentration due to increased water reabsorption

MAIN CONSEQUENCE of SIADH?

Hyponatraemia

Symptoms caused by SIADH? (7)

``` Generalised weakness Poor mental function Nausea When Na+ concentration falls <110 mM you get: CONFUSION COMA DEATH ```

Causes of SIADH? (3, (3/2/1/2/0)

``` - CNS: SAH, stroke, tumour, TBI - Pulmonary disease: Pneumonia, bronchiectasis - Malignancy: Lung (small cell) - Drug related: Carbamezapine, SSRI - Idiopathic ```

Medical treatment and treatment target for SIADH?

Vaptans | Non-competitive V¬2 inhibitors

How do vaptans work

Non-competitive V¬2 inhibitors | Inhibit AQP2 synthesis and transport to collecting duct apical membrane, preventing renal water absorption

Short term treatment for SIADH?

Address the hyponatraemia, you would immediately restrict fluid, and in the long term use drugs which prevent vasopressin action in kidneys.