Endo 3 - Neurohypophysial Disorders Flashcards
On an MRI, how does the PPG look?
Bright spot
What are the 2 nuclei in relation to the PPG?
Supraoptic nuclei and paraventricular nuclei
What 2 hormones does the PPG secrete?
Oxytocin and ADH/Vasopressin
What does ADH do?
Increases water reabsorption from renal cortical and medullary collecting ducts, via V2 receptors
Where are osmoreceptors located?
What do the osmoreceptors project onto?
Located in organum vasculosum
Project onto hypothalamic supraoptic and paraventricular nuclei
How is VP release brought about by osmoreceptors?
- Increased extracellular Na conc
- Causes osmoreceptor to lose water and osmoreceptor shrinks
- Causes increased osmoreceptor firing
- VP release from PVN and SON neurones
How does increased water reabsorption from Renal CD impact urine osmolality (and volume) and serum osmolality?
Urine Volume = decreases
Urine osmolality = increases
Serum osmolality = decreases
What is diabetes insidious caused by?
Insufficient ADH or ADH unable to work
What are the 2 types of Diabetes insipidus and explain their characteristics
- Cranial / central (absence/lack of circulating VP)
2. Nephrogenic (kidneys resistant to VP)
Which is the more common form of diabetes insidious, cranial or nephrogenic?
Cranial is more common
Name 5 causes of acquired cranial diabetes insipidus
- Traumatic brain injury
- Pituitary surgery
- Pituitary tumours, craniopharyngima
- Metastasis to pituitary gland (e.g. breast)
- Infiltrative disease of median eminence (e.g. TB / sarcoidosis)
What is more common, acquired cranial diabetes insipidus or congenital cranial diabetes insipidus
Acquired cranial diabetes insipidus
What drug is given to treat bipolar disorder?
Lithium
What are congenital causes of nephrogenic diabetes insipidus?
Mutation in gene encoding V2 receptor / AQP2 water channel
RARE
What are acquired cause of nephrogenic diabetes insipidus?
Lithium
What are the signs and symptoms of diabetes insipidus?
- Polyuria
- Hypo-osmolar urine
- Polydipsia
- Dehydration if fluid intake not maintained - can cause death
- Disruption to sleep
Give an example of medications that can cause a dry mouth
Anti-cholinergic medications
What is the difference between psychogenic polydipsia and DI?
Psychogenic polydipsia does not involve a problem in secreting VP.
IE psychogenic polydipsia they drink and urinate a lot and have a higher urine osmolality than DI
What is the normal hydrated plasma osmolality range?
270 - 290 most/kg H2O
Above the reference range for plasma osmolality indicates?
Diabetes insipidus
Below the reference range for plasma osmolality indicates?
Psychogenic polydipsia
Why do patients with psychogenic polydipsia have a reasonable, but slightly lower urine osmolality when fluid deprived compared to normal?
Because they are drinking so much, the concentration gradient in the medulla is decreased
4 biochemical features of Diabetes insipidus? (sodium, urea, plasma osmolality, urine osmolality)
- Hypernatraemia
- Increased urea
- Increased plasma osmolality
- Low urine osmolality (hypo-osmolar urine / dilute)
Describe biochemical features of psychogenic polydipsia (sodium, plasma osmolality, urine osmolality)
- Mild hyponatraemia (excess water intake)
- Low plasma osmolality
- Low urine osmolality
How is cranial diabetes insipidus treated?
V2 agonist given - Desmopressin (DDAVP). Works in central diabetes insipidus
Why is normal VP not given?
V1 agonists would have other effects on vasculature which are not wanted
How is desmopressin administered?
- Nasally
- Orally
- SC
How does desmopressin affect urine?
Reduces urine volume
Increases urine concentration
Why must patients not be drinking large amounts of fluid when giving DDAVP?
Risk of hyponatraemia
Nephrogenic diabetes is a rare form of DI. How is it treated?
Thiazide diuretic
What is SIADH
Syndrome of Inappropriate ADH.
Plasma VP conc is inappropriately high for plasma osmolality
What are the plasma sodium levels and blood circulating volume in SIADH patients?
- Hyponatraemic
2. Euvolaemia
How is ANP involved in hyponatraemia and euvolaemia?
ANP secreted from Right atrium, causing natriuresis
This contributes to euvolaemia and hyponatraemia
What are the signs of SIADH?
- Raised urine osmolality, decreased urine volume (initially)
- Decreased plasma sodium conc mainly due to increased water reabsorption
What are the symptoms of SIADH?
Can be symptomless
If plasma sodium < 120mM, generalised weakness, poor mental function, nausea
If plasma sodium < 110mM, confusion leading to coma leading to death
What are the causes of SIADH?
- CNS - subarachnoid haemorrhage, stroke, tumour, TBI
- Pulmonary disease - pneumonia, bronchiectasis
- Malignancy - small cell lung carcinoma
- Drug related - carbamazepine, SSRI
- Idiopathic
How is SIADH treated
- Appropriate treatment, e.g. surgery if tumour
- Reduce immediate concern (e.g. hyponatraemia).
Immediate: fluid restriction
Long term: drugs preventing VP action in kidneys - e.g. demeclocycline / drugs to inhibit action of ADH - V2 receptor antagonists
What are vaptans?
Non competitive V2 receptor antagonists that promote aquaresis - renal water loss (as opposed to diuresis which involves electrolyte loss also)
VERY EXPENSIVE
How do vaptans work?
Inhibit AQP2 synthesis and transport to CD apical membrane - prevents renal water absorption
