Neurohypophysial disorders Flashcards
Where does vasopressin act?
Renal cortical and medullary collecting ducts
What are the principal actions of vasopressin?
Stimulates synthesis and assembly of aquaporin 2
Increased water transport
Increased water reabsorption- antidiuretic
Acts on V2 receptors
What are the other actions of vasopressin?
Vasoconstrictor activity- V1a
Corticotrophin release- V1b
Factor VIII and Von Willebrand factor release- V2
Central effects
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 central diabetes insipidus caused?
Damage to the neurohypophysial system: Injury Surgery Cerebral thrombosis Tumours Granulomatous infiltration of median eminence
Idiopathic
Familial (rare)
How is nephrogenic DI caused?
Familial (rare)
Drugs
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
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?
Polydipsia
What is psychogenic polydipsia?
Central disturbance that increases the drive to drink
What two tests do you use to distinguish between polydipsia, central and nephrogenic diabetes insipidus?
Fluid deprivation test
Desmopressin (DDAVP)
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
How can you quickly check if a patient can release vasopressin without waiting for them to become dehydrated?
IV saline stimulation
How does IV saline stimulation work?
IV saline quickly increases plasma osmolarity and stimulates AVP release. Normals, polydipsics and nephrogenics will show a rapid increase in plasma AVP which can be measured but central will show no change
What is the syndrome of inappropriate ADH (SIADH)?
The plasma vasopressin concentration is inappropriate for the existing plasma osmolarity
In SIADH, what happens due to the increase in water reabsorption?
You start to dilute the ions in plasma and you become hyponatraemic and there is a decrease in urine volume
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?
Tumours Neurohypophysial malfunction Thoracic disease (pneumonia) Endocrine disease (Addison's) Physiological- under normal conditions (hypovolaemia, pain and surgery) Drugs 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 (lithium, dimethyl chloritetracyline (DMCT))
What two receptors does vasopressin act on?
V1 and V2
Where are V1 receptors?
Vascular smooth muscle Non-vascular smooth muscle Anterior pituitary Liver Platelets CNS
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)
In terms of effectiveness, how does desmopressin compare to argipressin in the vasculature and kidneys?
IN vasculature, desmopressin < argipressin
In kidneys, desmopressin > argipressin
What is desmopressin used to treat?
Cranial diabetes insipidus
Nocturnal enuresis (bedwetting)
Haemophilia
What are unwanted effects of desmopressin?
Fluid retention and hyponatraemia
Abdominal pain
Headaches
Nausea
What does peptidergic mean?
Nerve cells or fibres that use small peptide molecules as their neurotransmitters
What is terlipressin, the V1 peptidergic agonist, used to treat?
Oesophageal varices (causes vasoconstriction)
What is felypressin used for?
It is added to anaesthetics that dentists use to prolong their action (and other local anaesthetics). IT causes vasoconstriction so will keep local anaesthetic in area for longer
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-peptide vasopressin analogues
What is tolvaptan and what is it used to treat?
V2 receptor antagonist and hyponatraemia associated with SIADH
What drug increases vasopressin secretion?
Nicotine
What drugs decrease vasopressin secretion?
Alcohol
Glucocorticoids
