Neurohypophysial disorders Flashcards
Neurohypophysis produce which 2 hormones
Difference in mechanism between adenohypophyis and neurohypophysis
Where does vasopressin act?
Vasopressin and Oxytocin
Adenohypophysis: neurosecretion occurs at ME.
Neurohypophysis: Neurosecretion occurs directly into post p.g
Renal cortical and medullary collecting ducts
What are the principal actions of vasopressin?
Stimulates synthesis and assembly of aquaporin 2– antidiuretic
Increased water transport
Increased water reabsorption- antidiuretic
Acts on V2 receptors
What are the other actions of vasopressin?
Osmoreceptors located where
What happens when low water
Vasoconstrictor activity- V1a
Corticotrophin release- V1b
Factor VIII and Von Willebrand factor release- V2
Central effects
Organum Vasculosum– project to hypothalamic PVN and SON
Osmoreceptor shrinks
Increased osmoreceptor firing
VP released from hypothalamic PVN and SON neurones
What is the action of oxytocin?
Constriction of myometrium at parturition
Milk ejection reflex
What happens if you lack oxytocin?
Nothing serious- effect is induced by something else
What happens if you lack vasopressin?
Diabetes insipidus
What are the two forms of diabetes insipidus?
Central (cranial)- Absence or lack of circulating vasopressin
Nephrogenic- Kidney resistance to vasopressin
How is cranial diabetes insipidus caused?
Damage to the neurohypophysial system:
Injury
Surgery-out
Metastasis to the pituitary gland– e.g breast
Pit Tumours, craniopharngioma
Granulomatous infiltration of median eminence e.g TB
Congenital (rare)
How is nephrogenic DI caused?
Familial (rare)– mutation in gene encoding V2 receptor, aquaporin 2 type water channel
Drugs e.g lithium
What are the signs and symptoms of diabetes insipidus?
Large volumes of urine- polyuria Very dilute urine- hypo-osmolar Thirst and increased drinking- polydipsia Dehydration Disruption of sleep Electrolyte imbalance
What is the cycle in diabetes insipidus?
If you are unable to make vasopressin, you can’t reabsorb water so this leads to an increase in urine excretion and a reduction in extracellular fluid volume. This will lead to an increase in plasma osmolarity so that will lead to osmoreceptors triggering vasopressin release and it will trigger thirst, this will lead to drinking, decrease in plasma osmolarity and expansion of extracellular fluid volume
What is psychogenic polydipsia?
Central disturbance that increases the drive to drink
Excess fluid intake (polydipsia) and excess urine output (polyuria) BUT unlike DI, ability to secrete vasopressin in response to osmotic stimuli is preserved.
What two tests do you use to distinguish between polydipsia, central and nephrogenic diabetes insipidus?
Fluid deprivation test
Desmopressin (DDAVP)– analogue of VP
What results in terms of urine osmolarity will you see in a fluid deprivation test of a normal person, someone with polydipsia and people with central and nephrogenic DI?
In a normal person, fluid deprivation will stimulate vasopressin system and they will release AVP and concentrate the urine so urine osmolarity increases and plasma osmolarity will remain normal
In polydipsia, vasopressin works fine so response is same as normal
In central/nephrogenic DI, there will be little or no change in urine osmolarity as vasopressin system doesn’t work
What results in terms of urine osmolarity would you see when DDAVP is administered to all patients?
Urine osmolarity will increase in normal, polydipsia and central DI but not nephrogenic because their receptors don’t respond to vasopressin anyway
Diabetes insipidus biochemical features Salt Urea Plasma osmolality Urine
Hypernatraemia
Raised urea
Increased plasma osmolality
Dilute- hypo osmolar urine- low urine osmolality
Psychogenic polydipsia biochemical features
Salt
Osmolality
Urine
Mild hyponatraemia -excess water intake
Low plasma osmolality
Dilute (hypo-osmolar) urine i.e low urine osmolality
What is the syndrome of inappropriate ADH (SIADH)?
The plasma vasopressin concentration is inappropriately for the existing plasma osmolarity
In SIADH, what happens due to the increase in water reabsorption from collecting duct?
Function of Atrial Natriuretic Peptide ANP
You start to dilute the ions in plasma and you become hyponatraemic and there is a decrease in urine volume
Expansion of ECF volume by increasing sodium excretion
What are the signs of SIADH?
Raised urine osmolarity
Decreased urine volume
Hyponatremia
What are the symptoms of SIADH?
Can be asymptomatic When Na concentration falls below 120mM: Generalised weakness Poor mental function Nausea When Na concentration falls below 110mM: Confusion Coma Death
What are the causes of SIADH?
CNS -SAH, stroke, tumour, TBI Pulmonary disease -Pneumonia, bronchiectasis Malignancy -Lung (small cell) Drug related -carbamazepine, SSRI Idiopathic
What is the treatment of SIADH?
Surgery- for tumours
If hyponatraemic, this needs to be dealt with immediately- Fluid restriction
Longer term- Use drugs that prevent vasopressin action in the kidneys Demeclocyline-induce nephrogenic DI
What two receptors does vasopressin act on?
V1 and V2
Where are V1 receptors?
Where are V2
V1 Vascular smooth muscle Non-vascular smooth muscle Anterior pituitary Liver Platelets CNS
V2
- Kidney
- Endothelial
What are effects of V1 receptors?
Vasoconstriction due to contraction of vascular smooth muscle
Affect the intestines by acting on non-vascular smooth muscle
What are Terlipressin and desmopressin?
Selective vasopressin receptor peptidergic agonists
What is Terlipressin?
Analogue of vasopressin but only has effects on V1 (Desmopressin only has effects on V2)
What is desmopressin used to treat?
Administered
Risk
Cranial diabetes insipidus
Reduction in urine volume
Nasally, orally, SC
Must tell patients to NOT to continue drinking large amounts of water– risk of hyponatraemia
What is nephrogenic diabetes insipidus treated with?
Thiazides e.g. bendroflumethiazide
What is the mechanism of action of thiazides?
Inhibits Na+/Cl- transport in distal convoluted tubule- this leads to a diuretic effect
Volume depletion leads to compensatory increase in sodium reabsorption at PCT
Increased proximal water reabsorption so decreased amount of water reaches DCT so reduced urine volume
What are vaptans?
Non-competitive v2 receptor antagonists
Action of vaptans
Treat
Disadvantage
Inhibit aquaporin 2 synthesis and transport to collecting duct apical membrane, preventing renal water reabsorption
-Aquaresis-solute-sparing renal excretion of water, contrast with diuretics (diuresis) which produce simultaneous electrolyte loss
Treat:
Hyponatraemia associated with SIADH
Expensive
If a patient has a plasma osmolarity above 290mOsm.kg H2O^-1, what do they have?
Diabetes insipidus
If a patient has a plasma osmolarity below 270 mOsm.kg H2O^-1, what do they have?
Psychogenic polydipsia
