Hypothalamus…proud mother; has twodaughtersAnterior pituitary [adenohypophysis]…is agland..having vascular connections with thehypothalamusPosterior pituitary [neurohypophysis]…is not agland but an extension of the
The adenohypophysis develops fromRathke’s pouch, which is an upwardinvagination of oral ectoderm from the roof ofthe stomodeum neurohypophysis develops from theinfundibulum, which is a downward extensionof neural ectoderm from the floor of the
the supraoptic and paraventricular nuclei ofthe hypothalamus (cell bodies of themagnocellular, neurosecretory neurons)the supraoptico-hypophyseal tractthe posterior pituitary
Situated in the pituitary fossa limitedanteriorly, posteriorly and inferiorly by bonyconstituents of the sella turcica [a depressionin the body of the sphenoid bone]Demarcated laterally and superiorly byreflections of dura and elsewhere by the sellaturcica
arterial blood supply from the inferiorhypophyseal artery [arises from themeningohypophyseal trunk, a branch of thecavernous segment of the ICA]SON and PVN: from thesuprahypophyseal, ACOM, PCOM, anteriorcerebral and posterior cerebral arteries, allderived from the circle of Willis.Venous drainage via the dural, cavernous and
Synthesis of the VP and OT precursorsoccurs in the cell bodies of magnocellularneurosecretory neurons within the SON &PVN of the hypothalamus They migrate along the axons & get stored insecretory granules within the terminals of themagnocellular neurons in the posterior
The osmoregulatory systems for thirst and VPsecretion, and the actions of VP on renalwater excretion, maintain plasma osmolalitywithin narrow limits: 284 to 295 mOsmol/kgthe mean plasma osmolality above whichplasma VP increases in response toincreases in plasma osmolality [osmoticthreshold for VP] is 284 mOsmol/kg ; relation
Reductions in circulating volume andhypotension stimulate VP release[baroregulation]Nausea and emesis.Manipulation of abdominal contents.osmoreceptors are situated in anteriorcircumventricular structures: the subfornicular organ
vasopressin exerts its antidiuretic effect via V2 receptors and involves insertion of protein water channels called Aquaporins [13 variants] vasopressin-responsive water channel in the collecting ducts is aquaporin-2• NB:AQP1: in apical and basolateral membranes of the PCT
Significant changes in secretion occur whenosmolality is changed as little as 1%Maximum diuresis at plasma VP conc of 0.5pmol/L or less.Maximum urine concentration achieved atplasma VP concentrations of 3-4 pmol/L
VP stimulates the expression of aquaporin onthe luminal surface of the interstitial cellslining the CD.Presence of aquaporin (AQP) in the wall ofthe distal nephron allows resorption of waterfrom the duct lumen along an osmoticgradient, and excretion of concentrated urine.
decrease medullary blood flow stimulate active urea transport in the distal CD stimulate active Na transport into the renal interstitiumAll these contribute to the generation andmaintenance of a hypertonic medullaryinterstitium, and this augment VP-dependentwater resorption.
Diabetes [Greek] = to go through[describing excessive urination]Insipidus [Latin] = without tasteMellitus = sweet urineDiabetes insipidus (DI) involves thepassing of urine that is tastelessbecause of its relatively low sodiumcontent.
Central --impaired AVP productionNephrogenic --due to refractoriness of thedistal nephron to the effects of AVP.
DI complicates the postoperative course occursin ̴ 30% of patients undergoing pituitary surgery,transient and relatively benign in the majority ofcasesChronic postoperative DI : incidence ̴ 0.5% to15% in neurosurgical reviews.This is relatively uncommon because >90% ofthe magnocellular AVP neurons in the SON &PVN must degenerate bilaterally before
Pre-operative central diabetes insipidus hasbeen reported in 8-35% of patients affectedwith craniopharyngioma, and in 70-90% aftersurgery.
Unusual for pituitary adenomas to presentwith DIThey are slow growing also…the site of AVP release shifts from theposterior pituitary to the median eminenceSeen as an upward migration of the posteriorbright spot by MRI
Clinical signs and symptoms Polyuria, high volumes (>2.5 -3.0 mL/kg/hr or 4–18 L/day), with abrupt onset, typically within 24–48 hours postoperatively• Polydipsia, with craving for cold fluids which better quenches osmotically- stimulated thirst• With/without hypovolemia, depending on whether the patient has an intact thirst mechanism Laboratory data Dilute urine (specific gravity less than1.005, urine osmolality less than 200 mOsm/kg H2O)• Normal to increased serum osmolality >295 mOsm/L• S[Na+] greater or equal to 145 milliequivalent/L with continued diuresis of hypotonic urine• Irritability or mental status changes, dehydration, shock
osmotic diuresis from glucosuria Is he getting stress doses of steroids? Excessive fluids intraoperatively• If this large postoperative diuresis is matched with continued intravenous fluid infusions, an incorrect diagnosis of DI may be made based on the resulting hypotonic polyuria; medullary washout phenomenon diuretic use (including mannitol) the recovery phase of acute renal failure primary polydipsia, and after relief of obstructive uropathy.
Therefore, if the serum [Na+] is not elevatedconcomitantly with the polyuria, the rate ofparenterally administered fluid should be slowedwith careful monitoring of the serum [Na+] and urineoutput until a diagnosis of DI can be confirmed bycontinued hypotonic polyuria in the presence ofhypernatremia or hyperosmolality
. withhold water: stimulates AVP rise in plasma Na Mild dehydration production urine output, should ↓, and urine water conservation osmolality, which should ↑
dangerous in ICU patientscan induce hypovolemia and hemodynamic instability.Further, ICU patients with DI often have already developed at least mildhypernatremia spontaneously, which obviates the rationale‘inappropriately low urine osmolality in the face of even very mildhypernatremia’: means at least partial DI is there
Normal response to hypernatremia: Urine osmolality >800 mOsmol/kg H2O . Response in partial DI: Urine osmolality 300–700g mOsmol/kg H2O Response in complete DI: urine osmolality <300 mOsmol/kg H2O
can be made by measuring plasma AVP levels after waterdeprivation or spontaneous development of mildhypernatremia
.Normal response to hypernatremia:Plasma AVPconcentration >2 pg/mLResponse in partial DI: Plasma AVP concentrationmay reach 1.5 pg/mLResponse in complete DI: Plasma AVP concentrationundetectable Response in nephrogenic DI: Plasma AVP concentration can exceed 5 pg/mL
More commonly achieved by assessing urineosmolality before and after a single dose ofaqueous AVP (5 units subcutaneously) or theAVP analog desmopressin (1 or 2 μgsubcutaneously or IV)The response in central DI may be blunted if there has beendown-regulation of aquaporin channels or a significantdegree of medullary washout
.Normal response: No more than a 5% increase inurine osmolalityResponse in partial central DI: 10–50% increase inurine osmolalityResponse in complete central DI: At least a 50%increase in urine osmolalityResponse in nephrogenic DI: No change in urineosmolality is expected
Bright spot in the sella can be visualized onT1-weighted images when stored vasopressinand oxytocin are present in neurosecretorygranules of the posterior pituitary.Absence ofthis bright spot is characteristic of DINot very reliable
classic studies of pituitary stalk transectiondescribes three types: transient, permanent,or triphasicTransient DI :begins within 24 to 48 hours ofsurgery and usually abates within severaldaysPermanent
. severing of the neuronal connections or axonal shock from perturbations in the vascular supply to the pituitary stalk temporary dysfunction of AVP producing neurons resolves as the vasopressinergic neurons regain full function.
Rarely persistent DI may follow as preformedstores of AVP are depleted and no additionalAVP is synthesized.
In a series of 24 patients*… 80% to 100% DI with higher stalk injurylow pituitary stalk section at thelevel of the diaphragmsella, only 62% developedpermanent DI * *Sharkey PC, Perry JH, Ehni G. Maclean JP, West CD, et al
First phase of DI typically lasts 5 to 7 daystransitions into a second antidiuretic phase ofSIADHcaused by the uncontrolled release of AVPfrom degenerating posterior pituitary tissue, orfrom the remaining magnocellular neuronswhose axons have been severed
Urine quickly becomes concentrated inresponse to the elevated plasma AVP levelsand urine output markedly decreases.Continued administration of excess waterduring this period can quickly lead tohyponatremia and hypoosmolality. can lastfrom 2 to 14 days .
After the AVP stores are depleted from thedegenerating posterior pituitary, the thirdphase of chronic DI then typicallyensues, although not alwaysIn this phase, there are insufficient remainingAVP neurons capable of synthesizingadditional AVP, thereby resulting in permanent
aprofound hypernatremia,hyperosmolality, and dehydration, Ifsufficient water intake or hypotonic IV fluid is not provided• unlikely if the total body water deficit is entirely due to electrolyte free water loss; very likely with even small degrees of co-existing total body sodium depletionHypokalemia, hypomagnesemia, and hypophosphatemia• Also should be anticipated
. Close monitoring of water balance (fluid intake and output) Urine osmolality or specific gravity every 4 to 6 hrs, until resolution or stabilization Frequent serial measurements of serum Na,K,Mg, and P concentration. Serum [Na+] every 4 to 6 hours, until resolution or stabilization Appropriate titration of IV fluids to prevent or correct volume depletion and hypernatremia
Avoid other causes of polyuriaDI = continued hypotonic polyuria despitehyperosmolality.criteria for subsequent redosing of ADHanalogues need not be as stringent, and canbe based simply on the redevelopment ofpolyuria
Allow patient to drink according to thirstSupplement hypotonic intravenous fluids(D5W to D5 1/2NSS) if patient is unable tomaintain a normal plasma osmolality andserum [Na+] through drinking
The established water deficit = 0.6 Xpremorbid weight X [1-140/serum Na(mmol/L)]Ongoing losses decrease the efficacy of thisformula
• NS or other isotonic In patients crystalloid given initially.. with severe • even if the patient is hypernatremic fluid depletion Then • more gradually to avoid intracellular inducing cerebral edema volume • particularly if significant hypernatremia has been depletion is + for >24 hrs corrected
even slow correction of the volume deficit maynecessitate a high rate of hypotonic fluidadministration if there is ongoing polyuria.Overhydration water diuresis medullarywashoutsustaining the polyuria even if the DIresolves.
Positive daily fluid balance >2 L suggestspossibility of inappropriate antidiuresisIf so antidiuretic hormone therapy should beheld and fluids restricted to maintain serum[Na+] within normal ranges
Any patient with postoperative DI, andparticularly those manifesting a triphasicresponse, should be assumed to haveanterior pituitary insufficiencyCover with stress dose corticosteroids(hydrocortisone 100 mg iv every 8hours, tapered to 15mg to 30mg by mouth
Aqueous AVP has a half-life of 2–4 hours andcan be given s/c, im,IV bolus, or by continuousIV infusion. It is a potent vasoconstrictor,owing toits effect on vascular V1 receptorsDose 4-10 units s/c or i.m. repeated every 4 to 6hoursrecommended only for diagnostic purposes or inacute conditions (e.g., trauma) in which the DI
Preparations PITRESSIN • 5u / mL im TANNATE • Q4-8H SYNTHETIC • 50 u / mL in isotonic saline LYSINE • DRODID nasal sprayVASOPRESSIN • 1-2µg bd iv or s/cDESMOPRESSIN • 10-20 µg bd/tid nasal spray • 200-600 µg bd / tid orally
1-deamino-8-D-arginine-vasopressinDesmopressin, initial dose of 1 μg to 2 μg i.v.or s/c dosed at 1–2 μg every 8–12 hours; half-life 8–20 hrs SPRAY INTRANASAL SOLUTION 100 UG/ML INTRANASAL 10 UG/SPRAY IM 4 UG/ML ORAL 200UG TAB<2 yr: 2-5ug intranasal; >2 y:5-10 ugrams/day
Parenteral routes are preferable, because thisobviates any concern about absorption, causesno significant pressor effects, and has the sametotal duration of action as the other routesRedose when urine output 200 mL to 250 mL perhour for greater than or equal to 2 hours, withurine specific gravity less than 1.005 or urineosmolality less than 200 mOsm/kg H2O
Prompt reduction in urine output and theduration of antidiuresis is approximately 6 to12 hours.Each dose of desmopressin should be givenafter the recurrence of polyuria, but before thepatient actually becomes hyperosmolar toavoid fluid retention and hyponatremia
Excretion of 200 mL to 250 mL per hour ofurine with an osmolality less than 200mOsm/kg H2O or specific gravity less than1.005 affirms the need for retreatment withdesmopressin
Dosing desmopressin on an as neededbasis, also has the benefit ofallowing the detection of return of endogenousAVP secretionor the start of the second phase of a triphasicresponse,by a lack of return of polyuria after the effects ofthe previous desmopressin dose have dissipated
intranasal or oral desmopressin.The nasal spray delivers metered single doses of0.1 mL (10 micrograms).The reliability diminishedin patients with mucosal atrophy, nasalcongestion, scarring, or nasal dischargeSo wait until several days postoperatively beforeusing intranasal desmopressin, especially inpatients who have nasal packing in place.
Duration 6 to12 hours: most patients requiretwice daily dosing.It is often useful to permit intermittent polyuricepisodes every 1 to 2 weeks by delaying adose of desmopressin, thereby verifyingcontinued presence of DI and allowing anyretained excess water to be excreted so that
Patients with chronic rhinitis or mucosal scarring:oral preparations more viable optionavailable in 0.1 mg to 0.2 mg dosing options20 times higher dose than intranasal spray as>99% of the oral dose is destroyed bygastrointestinal peptidases.central DI : on average 200 mg to 600 mg of oraldesmopressin two times per day to controlpolyuria
headache, nausea, nasal congestion,flushingand abdominal crampingno pressor effects because it selectively bindsto the AVP V2 receptorssafe in patients with coronary or hypertensivecardiovascular disease
Patient with DI coming for surgery dose intrajust before surgeryusualnasally or aq.vasopressin 100 mu iv bolusf/b constant infusion of 100-200 mu/hr[0.1mU/kg/hr]isotonic ivfsp.osmolarity hourly..closely monitor Naif >290 mosm/l hypotonic ivfs & increasevasopressin infusion >200 mu/ hr
. Stopping any causative drugs Monitoring fluid balance and electrolyte levels, Supplying IVFs restricting Na intake
. Na restriction and thiazides mild volume contraction stimulates sodium and water reabsorption in the PCT decreases water delivery to the distal nephron limit polyuria
• Especially when Li. Amiloride exposure is the cause +/- • amiloride limits lithium entry into tubular cells thiazide • Indomethacin and ibuprofen Others • Desmopressin;in those with receptor mutations high doses may be useful
Neurocritical Care ;Michel T. TorbeyDisorders of Water and Salt Metabolism Associated withPituitary Disease Jennifer A. Loh, MD, Joseph G.Verbalis, MD ; Endocrinology and Metabolism Clinics of NorthAmericaEndotext.org; Stephen G Ball, Peter H BaylissDiabetes insipidus in Craniopharyngoma; postoperativemanagement of water and electrolytes; StefanoGhiradello,Neil HopperBope and Kellerman: Conns Current Therapy 2012, 1st ed.
Well just mill around. till hes asleep, and then send him back up. This operation is actually for a placebo effect.
A particular slide catching your eye?
Clipping is a handy way to collect important slides you want to go back to later.