Neurohypophysial disorders

Question 1

How can the posterior pituitary be identified?

Answer 1

Bright spot at back of pituitary on MRI.

Question 2

Why is the posterior pituitary sometimes called the neurohypophosis?

Answer 2

It is derived from neural cells rather than glandular cells.

Question 3

Label diagram of hypothalamo-neurophypophysial system.

Answer 3

Question 4

What are the primary secretions of the posterior pituitary?

Answer 4

vasopressin and oxytocin.

Question 5

What is the principal effect of vasopressin?

Answer 5

Anti-diuretic: increase water reabsorption from renal cortical and medullary collecting ducts via V2 receptors.

Question 6

Label diagram outlining action of vasopressin at collecting duct.

Answer 6

Question 7

How do osmoreceptors aid plasma H2O regulation?

Answer 7

Osomoreceptors near hypothalamus. Project into PVN and SON which secrete vasopressin.

Question 8

Outline how osmoreceptors might regulate plasma H2O.

Answer 8

Increase in plasma Na+ leads to H2O osmosing out of osmoreceptors. Osmoreceptor shrinks –> increased firing rates –> increased VP release from PVN and SON neurons in hypothalamus.

Question 9

Outline the normal response to water deprivation.

Answer 9

Question 10

What 2 ways can vasopressin relate to diabetes insipidus?

Answer 10

Absence/lack of circulating vasopressin = central diabetes insipidus.

Organ resistance (kidneys) resistance to vasopressin = nephrogenic diabetes insipidus.

Question 11

What can cause central diabetes insipidus?

Answer 11

Traumatic brain injury

pituitary surgery

pituitary tumours (craniopharyngioma)

metastasis to pituitary gland

granulomatous infiltration of median eminence.

drugs - e.g. lithium.

congenital (rare)

Question 12

What can cause congenital diabetes insipidus?

Answer 12

e.g. mutation in gene encoding V2 receptor/ aquaporin 2 type water channel.

Question 13

List the signs and symptoms of diabetes insipidus.

Answer 13

Polyuria

Very dilute urine

Thirst (polydipsia)

Dehydration

Sleep disruption associated with polyuria and polydipsia.

Question 14

Outline the pathology of diabetes insipidus. How might it lead to death?

Answer 14

Failure to drink in response to polydipsia.

Question 15

Why is psychogenic polydipsia most frequently seein in psychiatric patients?

Answer 15

May reflect anti-cholinergic effects of medication creating a dry mouth sensation.

Patients being told to drink plenty by healthcare professionals.

Question 16

Outline the main features of psychogenic polydipsia.

Answer 16

Polydipsia + polyuria, but vasopressin system is functional, though not secreted due to high H2O intake.

Question 17

How can diabetes insipidus and psychogenic polydipsia be distingiushed?

Answer 17

DI = high plasma osmolality (>290 mOsm/kg H2O)

PP = low plasma osmolality (<270)

Question 18

How can DI and PP be distinguished with a fluid deprivation test (diagram)?

Answer 18

PP - increased urine osmolality.

DI - no change in urine osmolality.

Question 19

How can central and nephrogenic DI be distinguished with a fluid deprivation test?

Answer 19

DDAVP administration - VP analogue.

Leads to increased urine osmolality in central DI, nephrogenic DI stays low.

Question 20

List some biochemical features of DI.

Answer 20

Hypernetraemia.

Raised urea.

Increased plama osmolality.

Low urine osmolality.

Question 21

List some biochemical features of psychogenic polydipsia.

Answer 21

Mild hyponatraemia (due to excess water intake)

Low plasma osmolality.

Low urine osmolality.

Question 22

Why must vasopressin receptor peptidergic agonists be selective.

Answer 22

We have V1 and V2 receptors - activating V1 receptors would have effects in unwanted systems e.g. vascular smooth muscle, liver, platelets etc.

Drug must be specific for V2 receptors.

Question 23

Name a V1 and V2 vasopressin receptor peptidergic agonist.

Answer 23

V1 - terlipressin.

V2 - desmopressin (DDAVP).

Question 24

How can desmopressin be administered?

Answer 24

Nasally

Orally

Subcutaneous injection

Question 25

What effect does desmpressin have on central DI patients? What concern does this crease?

Answer 25

reduction in urine volume and concentration - patient must be told to sotp drinking large amounts to avoid hyponatraemia.

Question 26

How can nephrogenic DI be treated?

Answer 26

Thiazides, e.g. bendroflumethiazide.

Question 27

Outline the mechanism of action of thiazides.

Answer 27

–Inhibits Na+/Cl-transport in distal convoluted tubule(→diuretic effect)

–Volume depletion

–Compensatory increase in Na+ reabsorption from the proximal tubule (plus small decrease in GFR, etc.)

–Increased proximal water reabsorption

–Decreased fluid reaches collecting duct

–Reduced urine volume

Question 28

What is syndrome of inappropriate ADH (SIADH)?

Answer 28

Plasma vasopressin concentration is inappropriately high for plasma osmolality.

Question 29

Outline the pathology of SIADH (diagram).

Answer 29

Re

Question 30

List the signs and symptoms of SIADH.

Answer 30

signs:

raised urine osmolality, reduced urine volume.

hyponatraemia.

symptoms (if any):

p[Na+]<120mM –> generalised weakness, poor mental function, nausea.

p[Na+]<110 mM –> confusion leading to coma and death.

Question 31

List potential causes of SIADH.

Answer 31

CNS - sub-arachnoid haemorrhage, stroke, tumour, TBI

Pulmonary idsease - pneumonia, bronchiectasis.

Malignancy - lung

Drug-related - carbamazepine, selective serotonin reuptake inhibitors (SSRI)

Can be idiopathic.

Question 32

How is SIADH treated?

Answer 32

long term - surgery

immediate concern - fluid restriction, use drugs that reduce VP action in kidneys e.g. demeclocyline.

Question 33

What are Vaptans?

Answer 33

non-competitve V2 receptor antagonists.

Inhibit AQP2 syn. and transport, preventing renal H2O reabsorption.

Aquaresis - solute sparing H2O renal excretion.