Neurohypophysial Disorders Flashcards
Name the 2 main nuclei within which neurones of the neurohypophysis have their cell bodies.
Paraventricular Nucleus
Supraoptic Nucleus
What 2 hormones are produced by the neurohypophysis?
Vasopressin
Oxytocin
What is the principal action of vasopressin and how does it carry out this action?
Antidiuretic: increased water reabsorption from renal cortical + medullary collecting ducts via V2 receptors.
Stimulates synthesis of AQP 2, which is inserted into the apical membrane
State 5 other actions of vasopressin.
Vasoconstriction Corticotrophin release Factor VIII + von Willebrand factor Central effects Stimulates thirst
What are the main actions of oxytocin?
Contractile molecule that binds to oxytocin receptors
Causes contraction of the myometrium during parturition + is involved in milk ejection
It also has central effects
What are the consequences of a lack of the neurohypophysial hormones?
Lack of Oxytocin: not clinically significant
Lack of Vasopressin: Diabetes Insipidus
What are the 2 forms of diabetes insipidus?
Central (cranial): absence/ lack of circulating ADH
Nephrogenic: end-organ (kidneys) resistance to vasopressin
What can cause central diabetes insipidus?
Damage to neurohypophysial system (brain injury, pituitary surgery, metastasis to pituitary, pituitary tumours, granulomatous infiltration)
Familial (rare)
What can cause nephrogenic diabetes insipidus?
Familial (rare)
Drugs e.g. lithium, dimethyl chlortetracycline (DMCT)
State 5 signs and symptoms of diabetes insipidus.
Polyuria Polydipsia Hypo-osmolar urine Dehydration Possible disruption of sleep
State a cause of polydipsia that isn’t DM or DI
Psychogenic polydipsia
=a central disturbance that increases the drive to drink.
Frequently seen in psychiatric patients
What test can be used to distinguish between normal, psychogenic polydipsia, central DI and nephrogenic DI? Describe the results you would expect.
Fluid deprivation test
Normals + PP: Increase in urine osmolality
DI: little or no change in urine osmolality
Fluid deprivation with administration of DDAVP (Desmopressin)
CDI: Increase in urine osmolality
NDI: still have a low urine osmolality (end-organ resistance)
Describe plasma osmolality of someone with psychogenic polydipsia + someone with DI
PP: Plasma osmolarity lower than usual (as diluting plasma)
DI: Plasma osmolarity higher than usual (as passing out huge volumes of dilute urine)
Describe the normal change in urine osmolality as plasma osmolality increases.
Urine osmolality will increase as plasma osmolality increases (sigmoid shape graph)
In DI, there is little change in urine osmolality as plasma osmolality increases
What is SIADH?
Syndrome of Inappropriate ADH = plasma vasopressin concentration is inappropriately high for the existing plasma osmolality
State 3 signs of SIADH.
Decreased urine volume
Increased urine osmolality
Hyponatraemia (due to increased water reabsorption)
State some symptoms of SIADH that are caused by the hyponatraemia.
May be symptomless
Mild hyponatraemia = generalised weakness, poor mental function, nausea
Severe hyponatraemia = confusion, coma, death
State 5 causes of SIADH.
CNS (Stroke, Tumours) Pulmonary disease (pneumonia) Malignancy (lung) Drugs e.g. Carbamezipine Idiopathic
How is SIADH treated?
Appropriate treatment (e.g. surgery for tumour)
Fluid Restriction
Longer term: use drugs which prevent ADH action in kidneys
Which receptors do we want to target in treatment of CDI?
V2 receptors
Where are V1 and V2 receptors found?
V1: Vascular + non-vascular smooth muscle, Anterior pituitary, Liver, Platelets, CNS
V2: Kidney + Endothelial cells
Describe the administration, effects and precautions of Desmopressin in treatment of CDI
Admin: Nasally, Orally, SC
Effects: Reduces urine volume + increases concentration
Care: Stop drinking large amounts of fluid (risk of hyponatraemia)
State 2 selective peptidergic vasopressin selective agonists.
V1: Terlipressin
V2: Desmopressin (DDAVP)
State a treatment used for NDI and its possible mechanism of action.
Thiazide Diuretics (e.g. bendroflumethiazide)
Inhibits the Na+/Cl- pump in the DCT leading to a diuretic effect
This leads to volume depletion resulting in a compensatory increase in Na+ reabsorption from the PCT
This increases proximal water reabsorption so less water reaches the collecting duct
Ultimately leads to reduced urine volume
