Endo 3: Neurohypophysial disorders Flashcards
How does post. pit appear on MRI
Bright spot
2 hormones released from post pit
Oxytocin and ADH
Define diuresis
inrease urine producton
Outline principle effect of vasopressin
Increases water reabsorption from renal cortical and medular collecting ducts via V2 receptors
Outline principle effect of vasopressin
Increases water reabsorption from renal cortical and medular collecting ducts via V2 receptors
What regulates release of ADH
Osmoreceptors in organum vasculosum sensitive to plasma osmolality. These project to paraventricular and supraoptic neurons
Mechanism of osmorecepor action
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)
Outline normal response to water deprivation
Due to VP release, increased water reabsorption from renal collecting ducts –> reduces urine volume, increase in urine osmolality
What is diabetes insipidus
Absence of lack of circulating ADH
2 types of diabetes insipidus
Cranial (=central)= can’t make enough ADH problem with pituitary
Nephrogenic= kidneys resistant to vasopressin
Aetiology of cranial DI
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
Aetiology of nephrogenic DI
Congenital: rare (mutation in gene encoding V2 receptor, aquaporin 2 type water channel
Acquired: drugs (due to lithium drug to treat bipolar)
Presentation of DI
Polyuria, dilute urine (hypo-osmolar),
Presentation of DI
Polyuria, dilute urine (hypo-osmolar), polydipsia, DEHYDRATION (and consequences) if fluid intake not maintained can lead to death, sleep disruption
What is psychogenic polydipsia
In psychiatric patients perhaps due to anti-cholingeric effect of medication (‘dry mouth’). Ability to secrete vasopressin in response to osmotic stimuli preserved
Mechanism of psychogenic polydipsia
Increased drinking, expansion of EC volume decrease osmolality, less VP, less reabsorption, EC fluid volume returns to normal but large volumes of dilute urine
Normal plasma osmolality- where would DI or psychogenic polydipsia lie
270-290mOsm/kg H2O, DI above, Psychogenic polydipsia below
Why will a patient with a psychogenic polydipsia have a lower urine osmolality when fluid deprived
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)
Why will patient with DI have normal urine osmolality despite being fluid deprived in a water deprivation test
Lack of response/production of ADH means you can’t reabsorb water and therefore can’t concentrate urine
How can you differentiate between cranial and nephrogenic when giving DDAVP in a water deprivation test?
cranial- they will concentrate urine if given ADH
Nephrogenic- still can’t concentrate urine even if given synthetic ADH
Biochemical features of DI
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.
Psych polydips biochemical features
Mild hyponatramiea, low plasma osmolarity and dilute urine
How to treat cranial DI
V2- desmopressin (DDAVP) is v2 receptor agonist (nasal/oral or SC), reduces urine volume and urine concentration in cranial DI
What is terlipressin
NOT used to treat cranial DI, used to treat GI bleed bcause it acts on v1 receptor so vasoconstrictor
Danger with desmopressin (DDAVP)
if they carry on drinking loads of water, then they’ll reabsorb lots of water and become hyponatraemic
Treatment of nephorgenic diabetes insipidus
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
Difference between selectivity of vasopressin and DDAVP
DDAVP selective for V2, vasopressin for both
What is syndrome of inappropriate ADH (SIADH)
Plasma vasopressin concentration inappropriately high for existing plasma osmolality –> hyponatraemic
SIADH patients are usually hypervolaemic t/f
f: usually euvolaemic (due to ANP being released which makes you pass sodium)
Signs and symptoms of SIADH
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
Treatment of SIADH
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
What are vaptans
non compettive V2 receptor agonists cause aqauresis (which is getting rid of water rather than sodium)
Explain how vasopressin works at the cellular level
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.
Causes of SIADH
CNS
SAH, stroke, tumour, TBI
Pulmonary disease
Pneumonia, bronchiectasis
Malignancy
Lung (small cell)
Drug-related
Carbamazepine, SSRI
Idiopathic
