3. Neurohypophyseal Disorders Flashcards
Hypothalamo- Neurohypophysial system
Principle Actions of Vasopressin
- Acts on the renal, cortical and medullary collecting ducts
- Stimulates synthesis and assembly of aquaporin 2
- Increased water transport and WATER REABSORPTION
- This has an antidiuretic effect
- This occurs by action on V2 RECEPTORS
Other Actions:
- Vasoconstrictor activity- V1a
- Corticotophin (ACTH) release- V1b
- Factor VIII and von Willebrand Factor- V2
- Central effects
Principle actions of Oxytocin
- Constriction of myomentrium at parturition (uterine wall)
- Milk ejection reflex
- Acts via Oxytocin receptors
Effect of Oxytocin deficiency
Parturition and milk ejection effects are induced/ replaced by other means (not that dramatic)
Effect of vasopressin deficiency
DIABETES INSIPIDUS
Classification of diabetes insipidus
Can be one of TWO forms:
- CENTRAL (cranial)- abscence or lack of circulating vasopressin
- NEPHROGENIC- end organ (kidney) resistence to vasopressin
Causes of central diabetes insipidus
Damage to neurohypophysial system
- surgery
- cerebral thrombosis
- tumours (intrasellar or suprasellar)
- granulomatous infiltration of median eminence
Idiopathic
Familial (rare) usually receptor gene mutations
Causes of nephrogenic diabetes insipidus
Familial (rare)
Drugs- e.g lithium, DMCT
Signs and Symptoms of DIabetes Insipidus
- Large volumes of urine (polyuria)
- Very dilute urine (hypo-osmolar)
- Thirst and increased drinking (polydipsia)
- Dehydration (and consequences) if fluid intake is not maintained
- Possible disruption of sleep with associated problems
- Possible electrolyte imbalance
Cycle in diabetes insipidus
A lack of vasopressin causes an increase in urine excretion and a reduction in extracellular fluid volume
This leads to an increase in plasma osmolarity- osmoreceptors trigger vasopressin release triggering thirst
As a result the patient may present with normal plasma osmolarity if they are well hydrated
POLYDIPSIA- large volumes of urine and increased drinking
Plasma osmolarity in diabetes insipidus and polydipsia
DIABETES INSIPIDUS= 290 mOsm.kg H20-1
POLYDIPSIA= 270 mOsm.kg H20-1
Psychogenic Polydipsia
There is a central disturbance and this increases the drive to drink
Fluid deprivation test
This should stimulate the vasopressin system- a normal person will release AVP (arginine vasopressin) and concentrate the urine
Fluid deprivation test in psychogenic polydipsia
The vasopressin system is working fine so when they are dehydrated they will release vasopressin and concentrate the urine
- The urine osmolarity is slightly lower than in a normal person because over a long period of time you will start to loose the osmotic gradient necessary for AVP to exert its antidiuretic effect
Fluid deprivation effects in central and nephrogenic diabetes insipidus
There will be little or no change in urine concentration
Desmopressin (DDAVP) (+ clinical uses)
An alternative (ANALOGUE) to vasopressin
Effective in a person with polydipsia and CENTRAL diabetes insipidus because the receptors can be stimulated by DDAVP
It will not be effective in patients with nephrogenic diabetes insipidus because they already have normal vasopressin levels
Can be adminitered nasally or orally
Clinical uses:
- Cranial diabetes insipidus
- Nocturnal eneuresis (bedwetting)
- Haemophilia (need V2 stimulation)
How does urine osmorality change with plasma osmolarity
As someone becomes more and more dehydrated, their plasma osmolarity AND urine osmolarity should both increase considerably
Stimulation with hypertonic saline IV
- Used where you can measure plasma vasopressin
You can give the patient hypertonic saline I.V and this quickly increases plasma osmolarity and should stimulate AVP release
- Normal, polydipsics and patients with nephrogenic diabetes insipidus will show a rapid increase in plasma vasopressin
- Patients with Central diabetes insipidus will show NO CHANGE in plasma vasopressin
Characteristics, signs and symptoms of the Syndrome of Innapropriate ADH (SIADH)
The plasma vasopressin concentration is INNAPROPRIATE for the existing plasma osmolarity
Raised vasopressin despite normal or low plasma osmolarity leads to:
- Decreased urine volume
- Raised urine osmolarity
- HYPONATRAEMIA- decrease in plasma sodium concentration due to increased water reabsorption
Symptoms of SIADH:
- Can be asymptomatic
- When Na+ conc. falls <120mM
- Generalised weakness
- Poor mental function
- Nausea
- <110mM
- CONFUSION, DEATH, COMA
Causes of SIADH
- Tumours (ectopic secretion)
- Neurohypophysial malfunction (e.g meningitis, cerebrovascular disease)
- Thoracic disease (pneumonia)
- Endocrine disease (e.g Addison’s disease)
- Drugs
- Idiopathic
- Physiological
Treatment of SIADH
Once the cause (e.g tumour) is identified, you can undergo surgery
HOWEVER, if someone is already hyponatreamic:
- Immediate: fluid restriction
- Longer term: use drugs that prevent vasopressin action in the kidneys (e.g) DMCT
Pharmacological actions of argipressin
Argipressin is the term used for exogenous vasopressin (arginine vasopressin)
- Natriuresis (Na+ excretion)
- An unexplained effect of large amounts of vasopressin
- V2 mediated
- Only occurs when given high doses
- Pressor Action
- V1 mediated
- Not all vascular beds are equally sensitive
- The coronary vessels are particularly sensitive to vasopressin
- can cause ischaemia or angina attacks
- Other Actions
- V1a- gut motility
- V1b- ACTH
- V2- Von Willebrand factor production
V1 selective vasopressin receptor agonist (peptidergic)
Terlipressin- analogue of vasopressin but essentially only has V1 effects
V2 selective vasopressin receptor agonist (peptidergic)
Desmopressin
