Endocrinology 3- Neurohypophysial Disorders Flashcards
How does vasopressin increase water reabsorption?
- Binds to V2 receptor which results in aquaporin 2 synthesis
- Aquaporin 2 is inserted in the apical membrane, water travels in the cell.
How is vasopressin release regulated?
- By osmoreceptors in the organum vasculosum (project to paraventricular nucleus and supraoptic nucleus
- Osmoreceptors shrink in hypertonic solution (as high Na+ conc in extracellular fluid has lower water potential). This stimulates osmoreceptor firing (PVN and SON)
What is diabetes insipidus and what are the two types?
- Absense or lack of circulating vasopressin is cranial
- Kidney resistance is nephrogenic (very rare)
List the causes of cranial diabetes insipidis
- Usually acquired
- Damage to the neurohypophysial system
- Traumatic brain inury
- Pituitary surgery
- Pituitary tumours
- Metastasis of pituitary gland
- Granulomatous infiltration of median eminence (TB or sarcoidosis)
- Can be congenital
List the signs and symptoms of diabetes insipidus
- Polyurea (lots of wee)
- Urine very dilute - hypo-osmolar
- Thirst and increased drinking (polydipsia)
- Dehydration if fluid intake is not maintained - can lead to death
- Disruption of sleep
What is psychogenic polydipsia?
- Seen in psychiatric patients
- Also called primary polydipsia
- Patients have excess fluid intake (polydipsia) and excess urine input (polyuria) but vasopressin is normal
- Patients told to drink plenty by healthcare professionals, and drugs cause a dry mouth
List the biochemical features of diabetes insipidus
- Hypernatraemia
- Raised urea
- Increased plasma osmolality
- Low urine osmolality
List the biochemical features of psychogenic polydipsia
- Mild hyponatraemia (excess water)
- Low plasma osmolality
- Dilute urine
What are the selective vasopressin receptor agonists?
Terlipressin binds to V1 (blood vessels)
Desmopressin (DDAVP) binds to V2 (kidney)
(Vasopressin will bind to both so is useless)
Describe the administration and effect of desmopressin
- Administered orally, nasally or subcutaneous
- Reduced urine volume and concentration in cranial diabetes insipidus
- Patients shouldn’t continue to drink large amounts of fluid (hyponatraemia)
How are thiazides effective in treatment of nephrogenic diabetes insipidus?
- Inhibits Na+/CL- transport in distal convoluted tubule (diuretic)
- Volume depletion
- Compensatory increase in Na+ reabsorption from proximal tubule, and increased water reabsorption
- Decreased fluid reaches the collecting duct
What is syndrome of innapropriate ADH?
- ADH levels are inappropriately high for the plasma osmolality
- Results in increased ECF volume, atrial natriuretic peptide production and as a result hyponatraemia
List the signs of SIADH
- High urine osmolality
- Decreased urine volume
- Decreased sodium (hyponatraemia) mainly due to increased water reabsorption
List the symptoms of SIADH
- Symptomless
- Sodium concentration below 120mM results in weakness, poor mental function and nausea
- Below 110mM confusion leading to coma and then death
List the causes of SIDAH
- SAH, stroke, tumour or TBI
- Pulmonary diseases such as pneumonia
- Lung cancer (small cell)
- Can be drug related (carbemazepine, selective serotonin reuptake inhibitor)
- Can be idiopathic
List the treatments of SIADH
- Immediately fluid restriction is used
- Treat the underlying cause (eg. surgery for a tumour)
- Longer term drugs that suppress vasopressin activity are used (demeclcyline or V2 receptor antagonists)
What are vaptans?
- Non competitive V2 receptor antagonists
- Inhibit aquaporin 2 synthesis and transport and transport to the collecting duct apical membrane, preventing renal water reabsorption
- Aquaresis - renal excreton of water with no elecrolyte loss
- Very expensive drug
How is the posterior pituitary seen on MRI?
As a bright spot
Which hormones are produced by the posterior pituitary?
Vasopressin (ADH) and oxytocin
List the causes of nephrogenic diabetes insipidus
- Congenital (mutation in gene encoding V2 or aquaporin type 2)
- Acquired (lithium)
How can diabetes insipidus lead to death?
- Inadequate production/response to vasopressin
- Large volumes of hypotonic urine
- Increase in plasma osmolarity
- Reduction in EC fluid volume resulting in thirst (polydipsia)
- Drinking results in increase in EC fluid volume
- However, if a patient has undiagnosed diabetes insipidus has no access to water (eg. if they had a stroke and couldn’t drink) then they will die.
How is diabetes insipidus diagnosed?
- Water deprivation test
- Normal fluid deprived people and psychogenic polydipsia patients will have little or no concentrated urine
- In diabetes insipidus, urine will continue to be produced in large volumes and very dilute (central and nephrogenic)
- Bodyweight needs to be measured regularly (3% reduction means dehydration)
- Vasopressin test then distinguishes between cranial and nephrogenic - central will then concentrate urine, nephrogenic will not
How is nephrogenic diabetes insipidus treated?
Thiazides (diuretic)
