Endo 3: Neurohypophysial disorders

Question 1

How does post. pit appear on MRI

Answer 1

Bright spot

Question 2

2 hormones released from post pit

Answer 2

Oxytocin and ADH

Question 3

Define diuresis

Answer 3

inrease urine producton

Question 4

Outline principle effect of vasopressin

Answer 4

Increases water reabsorption from renal cortical and medular collecting ducts via V2 receptors

Question 5

Outline principle effect of vasopressin

Answer 5

Increases water reabsorption from renal cortical and medular collecting ducts via V2 receptors

Question 6

What regulates release of ADH

Answer 6

Osmoreceptors in organum vasculosum sensitive to plasma osmolality. These project to paraventricular and supraoptic neurons

Question 7

Mechanism of osmorecepor action

Answer 7

Increase osmolality, water flows out of osmoreceptor, it shrinks changes shape, stimulating increased firing rate, which stimulates release of ADH from hypothalamic nuclei (supraoptic and paraventricular)

Question 8

Outline normal response to water deprivation

Answer 8

Due to VP release, increased water reabsorption from renal collecting ducts –> reduces urine volume, increase in urine osmolality

Question 9

What is diabetes insipidus

Answer 9

Absence of lack of circulating ADH

Question 10

2 types of diabetes insipidus

Answer 10

Cranial (=central)= can’t make enough ADH problem with pituitary
Nephrogenic= kidneys resistant to vasopressin

Question 11

Aetiology of cranial DI

Answer 11

Acquired: damage to neurohypophysial system
-traumatic brain injury, pituitary surgery, pituitary tumour incl. craniopharyngioma, metastasis to pituitary gland eg breast, granulomatous infltration of median eminence e.g. TB or sarcoidosis
Congenital: rare

Question 12

Aetiology of nephrogenic DI

Answer 12

Congenital: rare (mutation in gene encoding V2 receptor, aquaporin 2 type water channel
Acquired: drugs (due to lithium drug to treat bipolar)

Question 13

Presentation of DI

Answer 13

Polyuria, dilute urine (hypo-osmolar),

Question 14

Presentation of DI

Answer 14

Polyuria, dilute urine (hypo-osmolar), polydipsia, DEHYDRATION (and consequences) if fluid intake not maintained can lead to death, sleep disruption

Question 15

What is psychogenic polydipsia

Answer 15

In psychiatric patients perhaps due to anti-cholingeric effect of medication (‘dry mouth’). Ability to secrete vasopressin in response to osmotic stimuli preserved

Question 16

Mechanism of psychogenic polydipsia

Answer 16

Increased drinking, expansion of EC volume decrease osmolality, less VP, less reabsorption, EC fluid volume returns to normal but large volumes of dilute urine

Question 17

Normal plasma osmolality- where would DI or psychogenic polydipsia lie

Answer 17

270-290mOsm/kg H2O, DI above, Psychogenic polydipsia below

Question 18

Why will a patient with a psychogenic polydipsia have a lower urine osmolality when fluid deprived

Answer 18

Excessive drinking reduces conc gradient in the medulla so they cant reabsorb quite as much water so it’s a little bit less (minor effect)

Question 19

Why will patient with DI have normal urine osmolality despite being fluid deprived in a water deprivation test

Answer 19

Lack of response/production of ADH means you can’t reabsorb water and therefore can’t concentrate urine

Question 20

How can you differentiate between cranial and nephrogenic when giving DDAVP in a water deprivation test?

Answer 20

cranial- they will concentrate urine if given ADH

Nephrogenic- still can’t concentrate urine even if given synthetic ADH

Question 21

Biochemical features of DI

Answer 21

Hypernatraemia, raised urea, increased plasma osmolality (all 3 due to dehydration), dilute urine. This could not be the case if they are keeping up with lots of drinking water- urine will deffo be dilute tho.

Question 22

Psych polydips biochemical features

Answer 22

Mild hyponatramiea, low plasma osmolarity and dilute urine

Question 23

How to treat cranial DI

Answer 23

V2- desmopressin (DDAVP) is v2 receptor agonist (nasal/oral or SC), reduces urine volume and urine concentration in cranial DI

Question 24

What is terlipressin

Answer 24

NOT used to treat cranial DI, used to treat GI bleed bcause it acts on v1 receptor so vasoconstrictor

Question 25

Danger with desmopressin (DDAVP)

Answer 25

if they carry on drinking loads of water, then they’ll reabsorb lots of water and become hyponatraemic

Question 26

Treatment of nephorgenic diabetes insipidus

Answer 26

Very rare type of DI- Thiazides

Thiazides normally increase diuresis by blocking the transporter which brings Na+ out of the filtrate, this increases Na+ concentration in the filtrate, reducing concentration gradient between filtrate and the ECF. So less water is reabsorbed and you get diuresis.

But a compensatory mechanism for this might be increase reabsorpiton of Na+ at the PCT, increased PCT water reabsorption, so decreased fluid reaching the collecting duct and reduced urine volume

Question 27

Difference between selectivity of vasopressin and DDAVP

Answer 27

DDAVP selective for V2, vasopressin for both

Question 28

What is syndrome of inappropriate ADH (SIADH)

Answer 28

Plasma vasopressin concentration inappropriately high for existing plasma osmolality –> hyponatraemic

Question 29

SIADH patients are usually hypervolaemic t/f

Answer 29

f: usually euvolaemic (due to ANP being released which makes you pass sodium)

Question 30

Signs and symptoms of SIADH

Answer 30

Sign: raised urine osmolality, decreased urine volume initially, hyponatraemia (due to increased water reabsorption)
Symptoms: can be asymptomatic, if [Na+] less than 120mM, generalised weakness, poor mental function adn nausea. If less than 110mM, confusion leading to coma and death

Question 31

Treatment of SIADH

Answer 31

Immediate- fluid restriction
Longer term: drugs which prevent vasopressin action in kidneys, e.g. induce nephrogenic DI and reduce renal water reabsorption called demeclocycline.
Or inhibit action of ADH= V2 receptor antagonists

Question 32

What are vaptans

Answer 32

non compettive V2 receptor agonists cause aqauresis (which is getting rid of water rather than sodium)

Question 33

Explain how vasopressin works at the cellular level

Answer 33

In collecting duct cells (principle), vasopressin binds to V2 receptors, this activates a Gs receptor, so AC converts ATP–>cAMP, which upregulated PKA which increases synthesis of AQP2. Aggraphores (collections of the AQP2 molecules) migrate to apical membrane, and are inserted here, increasing water reabsorption, reducing diuresis.

Question 34

Causes of SIADH

Answer 34

CNS
SAH, stroke, tumour, TBI

Pulmonary disease
Pneumonia, bronchiectasis

Malignancy
Lung (small cell)

Drug-related
Carbamazepine, SSRI

Idiopathic