| What is the physiology of ADH/ Vasopressin/AVP? | It is secreted by hypothalamus, stored in posterior pituitary, released when stimulated into blood vessels towards two targets, renal V2 receptors (increase H2O permeability in collecting ducts thus increasing H2O retention)
And vascular V1 receptors (causing increased arterial BP by increased total vascular resistance) |
| What is DI? | Diabetes insipidus (large amount of urine produced that is dilute, hypotonic and tasteless.
Caused by absence of ADH or inadequate response to it. |
| What are the 4 syndromes of DI? | Primary polydipsia (pathophysiology of excess water intake, may be due to increased thirst by an abstruction of hypothalamus or damage to it causing this increased thirst)
Hypothalamic DI (Pathophysiology of decreased synthesis or secretion of ADH)
DI of pregnancy (pathophysiology of accelerated metabolism of vasopressin due to vasopressinase in placenta)
Nephrogenic DI (pathophysiology of lack of appropriate response to vasopressin by kidney, due to receptor issue (genetic...)) |
| How is the presentation of DI? | Most pt have intact thirst mechanism (no dehydration but polyuria and polydipsia (increased thirst))
Severe hypernatremia (not observed in pt with DI because of intact thirst), however pt with inadequate thirst response can rapidly become dehydrated and develop hypernatremia
Hypertonic (hypernatremic) encephalopathy (coma, shrinkage of brain, seizures) may occur due to secretion of intracellular water towards outside where we have hypernatremia.
Decreased brain volume (subarachnoid hemorrhage, intracerebral bleed, petechial hemorrhage) |
| What is the typical clinical presentation of DI? | Polyuria/polydipsia immediately after brain surgery or after head trauma -->think hypothalamic DI. |
| What is the presentation of hypothalamic DI? | Sudden onset of symptoms (thirsty day and night)
Serum Na+ higher than normal
Serum uric acids elevated due to decreased renal clearance of urate
Urine volume (6-12 L/day)
modest dehydration and increased GFR
Elevated plasma osmolality |
| What is primary polydipsia? | Serum Na+ in low range, modest volume expansion, intermittent secretion of vasopressin (act on V1 to clear urate, so low uric acid serum)
Urine volume >18L
Plasma osmolality is low-range |
| What are the labs done to see DI? | 24 hour urine collection (determining urine volume)
Serum electrolytes, glucose and uric acid
Urinary specific gravity (DI <1.005)
Plasma osmolality (DI >287 mOsm/kg)
urinary osmolality (DI <200 mOsm/kg)
plasma ADH (not very useful since ADH has a low half-life)
Gold standard test is dehydration test |
| What is water deprivation test? | First we water deprive pt, then admin vasopressin/desmopressin
Water deprivation (urinary osmolality 2-4 times greater than plasma in healthy individual, and with admin of ADH we have an increase less than 9% in urinary osmolality)
In hypothalamic DI (we have a significant increase in urine osmolality after ADH administration) |
| How is the diagnosis of neurogenic DI? | Water deprivation results (after deprivation <300 urine osmol, after desompressin >800)
Absent white spot on MRI of sella |
| When does neurogenic DI usually occur? | It need 90% of vasopressinergic neurons to be destroyed in order to give symptomatic DI
For a mass lesion to cause it, it must destroy large area of hypothalamus, or be located at tracks at base of hypothalamus or top of pituitary stalk, or disease of pituitary stalk
So usually we have thickening of pituitary stalk with absence of white spot and search for systemic disease associated with it (germinoma, craniopharyngioma, granulatmatos, TB, metastasis...) |
| What are the causes of central DI? | Genetic abnormality of vasopressin gene (familial DI)
(occurs in childhood, polyuria, due to abnormal folding of vasopressin it accumulates in ER of neurons, genetic testing done to diagnose.)
Mass lesion of neurohypophysis (craniopharyngioma, metastasis, lymphoma)
Granulomatous disease
Idiopathic
Autoimmune
Surgery or Trauma of neurohypophyseal system. |
| What is nephrogenic DI? | Renal resistance to vasopressin, plasma levels normal or elevated
Caused by CKD, familial mutation of V2R/ aquaporin-2 genes.
Drugs (litium, demeclocyclin (vasopressin antagonist)
Hypercalcemia hypokalemia
multiple myeloma/SCA/sjogren |
| How is the presentation of pt with nephrogenic DI? | High vasopressin, chronic dehydration, posterior pituitary may be depleted of vasopressin, bright spot may be lost
No effect of desmopressin on urine osmolality (stays low) |
| What is oxytocin physio? | functions in smooth muscle activation promoting let-down of milk, and partuition contraction
As for lactation (humans let down milk by suckling (but may be without it like hearing a crying baby alone...), if oxytocin not secreted only 20-30% of stored milk is released)
As for parturition (increased oxytocin activity pushes fetus towards cervix) |
