renal siadh di csw

8/17/2019 Renal Siadh Di Csw

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SIADH, DI and Cerebral

Salt Wasting


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ADH

ADH is produced in

cells in the supraoptic

and paraventricular

nuclei

It is transported to and

released from the

posterior pituitaryDrain into cavernous

sinus and IVC

supraoptic

neurons

paraventricular

neurons

osmoreceptors

pons

barorecepto

input

ant.

ADH

pituitary post.


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Secretion of ADH

• Most importantvariable is osmoticpressure of plasmaand C!"# $argely a function of

the concentration of %a

• &smoregulationmediated byosmoreceptors in the

anteromedialhypothalamus nearthe suraoptic nucleus# 'lood supply is via

fenestrated capillaries,and so they are outside

'''

supraoptic

neurons

paraventricular

neurons

osmoreceptors

pons

barorecepto

input

ant.

ADH

pituitary post.


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ADH Secretion

• ADH also released in response tonon)osmotic variables

# Decrease in blood volume or arterialpressure of more than (4)*4+• .hese are mediated by neural pathays that

originate in pressure sensitive receptors in

the all of the $A and pro5ects via the vagaland glossopharyngeal nerves to the brainstem

# Have little function in normal physiologic states


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ADHcAMP

ATP

Prot

kinase

H2O

H2O

H2O

H2O

R ec

AC

Tubule

ADH Function

In the collecting duct

blood-borne ADH binds toa 2 receptor on the baso-

lateral sur!ace o! the

principal tubule cell.

"his stimulates adenylyl

cyclase to generate cA#$

and activate protein

%inases.

"his increases the

insertion o! &ater

channels' aquaporins'into the a ical sur!ace o!


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• When the collecting ducts arepermeable, ater 6lters don the

osmotic gradient in the medulla# 7lasma 8ADH9 beteen 4"0 and 0 pg"ml)

( accounts for the range of urineosmolalities i"e" (44 ) (*04 mosmol"3gH*&)("

• Without ADH, the collecting ductcells are impermeable to ater


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• ADH also acts on V( receptors, acting as avasopressor# .his causes an increase in e:ective plasmavolume, hich can then donregulate ADHsecretion through its action on the $Abaroreceptors

• V; receptors mediate AC.H secretion fromthe pituitary

• V* receptors also act to increase !actorVIII production


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Distribution and Clearance ofADH

• ADH circulates in an unbound stateand e


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ADH and .hirst= salt and aterbalance

• ADH function is limited, because itcannot prevent ater loss in e-cess

of that needed to e-crete a certainsolute load"# Another mechanism is needed to ensure

that these, and other losses arereplaced>• .HI?S.


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ADH and .hirst= salt and aterbalance

Plasma osmolality ≈ 290 mosmoles. kg H2O!.

&ater lac%

increased osmolality

e(cessive &ater inta%e

decreased osmolality

drin%ing

osmoreceptors

supraoptic

$) nucleisupraoptic

$) nuclei

lateral pre-

optic area

lateral pre-

optic area

ADH release

increasedADH release

reduced

thirst

enhanced

thirst

depressed

collecting duct

more permeablecollecting duct

less permeable

&ater retention

by %idneys

&ater loss

by %idneys

osmoreceptors


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Disorders of ADH secretion

or action


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Diabetes Insipidus


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Diabetes Insipidus

• Characteri@ed by# A large volume of urine diabetesB

# .hat is hypotonic, dilute and tastelessinsipidB• Versus the seet urine of diabetes mellitus

honeyB


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tiology

• !our fundamentally distinct defects# Central DI, a primary de6ciency of ADH

# %ephrogenic DI, caused by aninappropriate renal response to ADH

# .ransient DI of pregnancy, caused byvasopressinase produced by placenta

# 7rimary 7olydipsia, in hich pathology issecondary to ingestion, rather thanelimination of, uid


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Central DI

• Most common

• sually secondary to irreversible

destruction of EF4+ ADH producingneurons

• Genetic forms caused by

accumulation of poorly foldedprecursor proteins


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Genetic Congenital Ac


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Central DI

• In the &?2IC ) trauma# J year retrospective revie of all IC trauma

admissions

# DI secondary to trauma occurs as acomplication *"1+ of the time

# &verall mortality K1+

# All patients that died developed DI ithin the

6rst three days• Increased Mortality to FK+

'oughey,LC DI in the head in5ured patient, Am Sur5 Lun *44J


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Central DI

• Head .rauma# DI is often triphasic in nature

• (st phase, DI, occurs ithin *J hours of in5ury and is

due to a-on shoc3 and inability to propogate actionpotentials to the terminals in the post pit"

• *nd phase, antidiuretic phase, due to unregulatedrelease of ADH from posterior pituitary stores as thea-ons die

# .his phase can occur post head in5ury, ithout (st and;rd phases

• ;rd phase, return of DI, occurs after all the hormonehas been released


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Central DI

• In the IC2&? ) %eurosurg# &ccurs commonly in children ith

hypothalamic, pituitary or optic tumors

• Craniopharyngioma is the most common non)glialtumor in the pediatric age group

# DI develops in appro- F4+ of patients post)op

• &ccurs in /0+ of patients folloing pituitary tumorresection

# Most resolve post)op, K+ is permanent

Wise,$ 7erioperative management of DI in children, Lournal of%eurosurgical Anesthesiology Lan *44J


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%ephrogenic DI

• Caused by a poor response of the3idney to ADH

• Most common form is congenital• &ther forms are ac


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Genetic Ac


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7athophysiology

• $ac3 of ADH, or ADH response, leadsto a de6ciency in urine concentration

# ()*+ decrease in .'W, and a rise inplasma osmolality and %a• .he latter cause a thirst response, hich, if

intact, stabili@es osmos and %a

• 7olyuria further impairsconcentrating ability throughashout of medullary concentrationgradient


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Diagnosis

• $ots of stu: about uid restriction,ADH levels, DDAV7 trials, M?Is>"not

useful for us# seful for distinguishing beteennephrogenic and central forms• ndocrine consult

• .here is a much easier ay to gethat e need, and is based onsimple pathophysiology


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Diagnosis

• C$I%ICA$ SS7ICI&%# 'ad brain in5ury, neurosurg post)op

• High or increasing urine output# rine &smo usually N ;44m&sm23g

• Increasing serum %a

# Implies free ater loss in e-cess ofsodium loss, hich implicates ADH asthe culprit


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.reatment

• Vasopressin# 0)(4 mnits23g2hr# .itrate to a level that normali@es urine output and

stabili@es serum %a

• DDAV7# !or chronic correction# More resistant than vasopressin to degradation# 0)*4 micrograms2day by nasal spray

• &ral and SO forms available

• If nephrogenic# Sodium restriction and mild diuresis to encourage %aelimination

# Gene therapy in the or3s>""


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SIADH


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SIADH

• Characteri@ed by# Hypotonic hyponatremia

# impaired urinary dilution in the face ofhypoosmolality• rine osmolality E(44m&sm23g

# In the absence of=• Hypovolemia

• Hypotension

• Adrenal insuPciency

• 7rotracted emesis


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SIADH

• &ne of the most common causes ofhyponatremia in children and adults,

in the hospital setting


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tiology

ctopic 7ituitaryhypersecretion

%eoplasm

carcinoma of thebronchus, ovary, bladder mesothelioma

sarcoma

%eoplasm

carcinoma of bronchus

Drugs

DDAV7, vasopressin, o-ytocin

Drugs

carbama@epine, nicotine, .CA, MA&I, SS?I,vincristine

Head .rauma

Infections pneumonia, abcess of lung or brain, .',encephalitis, meningitis

7ulmonary

asthma, 7., 7&SI.IV 7?SS?V%.I$A.I&%

%eurologic

G'S, MS, hydrocephalus, cerebrovascularocclusion or hemorrha e


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• Most common causes# 7%A

# 'ronchiolitis# Asthma# 77V# C%S infections# Head trauma


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7athophysiology

• ADH cannot signi6cantly loer plasma %a, unlessater input E output

• When this occurs, the e-cess ADH ma3es a

ma3ing a dilute urine diPcult• Water accumulates in C! and IC! compartments

• Conc of %a and other solutes decreases

• ?enin and aldosterone activity decreases# Increases natriuresis as a response to e-pansion of C!

volume

• %atriuresis aggravates dilutional hyponatremia


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.he case against hypotonicmaintenance uids

• Many common etiologic agents causeSIADH

• Current recommendations for maintenanceuids are for hypotonic (2*%S

• SIADH Q hypotonic uids can lead to anacute and symptomatic hyponatremia

•E04 reported cases of neurologicmorbidity, including *K deaths, resultingfrom hospital ac


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• Children at greater ris3 forsymptomatic hyponatremia than

adults# ncephalopathy occurs at higher values

in 3ids• Higher brain to s3ull ratio leaves less room

for e-pansion


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• Morit@ et al, 7revention of hospital ac


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Di:erential Diagnosis

• SIADH must be di:erentiated fromhypervolemic, hypovolemic and otherforms of euvolemic hypernatremia

• Hypervolemic hyponatremia# Cirrhosis, CH!# Alays associated ith edema# &smotic regulation of ADH overhelmed by a

reduction in e:ective circulating volume, hichstims ADH release

# Secondary to hypovolemia, renin andaldosterone are increased, so there is nonatriuresis


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Di:erential Diagnosis

• Hypovolemic hyponatremia# Diuretic abuse, AG, mineralocorticoid

de6ciency# -cessive loss of %a and H*&

# Associated ith signs of hypovolemia=tachycardia, hypotension


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Diagnosis

•rine osmolality E(44m&sm23g of

ater during hypotonicity•rine sodium concentration EJ4m


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.reatment

• liminate the source""

• If not=

• If hyponatremia is mild and morethan JFhrs duration# Decrease uid inta3e belo insensible

losses, hich ill sloly increase %a"

# Watch for spontaneous remission ofSIADH• Can occur at any time, resulting in bris3

diuresis and a faster increase in serum %a

than desired


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.reatment

• If hyponatremia is severeaccompanied ith neuro symptomsB

or of less than JF hours duration# Slo ;+ infusion

# ?aise %a to point of cessation ofsymptoms

# After above, no faster than * m


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Cerebral Salt Wasting

Harrigan, Mar3 Cerebral salt wasting syndrome Critical CareClinics, Lan *44(


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De6nition

• A diagnosis of e-clusion

• ?e


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• So patient must not have# A physiologic cause for %a and Cl

e-cretion• an e-panded e:ective circulating arterial

volume

# A condition that may cause a de6ciency

of %a resorption• Aldosterone de6ciency

• diuretics


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7athophysiology

• %atriuretic !actors

• Direct %eural e:ects


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7athophysiology #%atriuretic !actors

• A%7# *F amino acid polypeptide

# :ects=• %atriuresis

• Diuresis

• Vasodilation

• Suppression of renin and aldosteronesecretion


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• A%7# ?eleased in response to atrial stretch

# C%S modulates A%7 secretion

• lesions of speci6c areas in hypothalamus decreasecardiac secretion of A%7 in response to volumee-pansion

• So, intracranial disease may lead to a disturbance inits control over A%7 secretion

# K2F neurosurg pts had elevated A%7 levels, ith acorrelation beteen A%7 level and degree ofhyponatremia

# After SAH, ADH and A%7 levels elevated on days 4)*,A%7 levels remained high after one ee3, hen ADHlevels declined SIADH and CSW may co)e-ist, complicating

diagnosis


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• A%7# Hoever>"

# A regression analysis of (0 patients ithCSW secondary to .' mening, foundplasma A%7 levels accounted for onlyK0+ of variation in plasma %a"

# .o other factors may play a role


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• '%7# &f cardiac ventricular origin

• Also locali@ed in hypothalamus

# Secreted in response to increased pressure orstretch

# Similar e:ects to A%7

# '%7 levels are elevated in patients ith SAH

# Acute intracranial disease may cause releaseof cardiac '%7, and hypothalamic damagemay also release '%7

• 7lasma %atriuretic factor# T


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A little more on '%7>>

• J4 patients ith SAH, '%7 levels measured# Change in, not absolute value of, '%7 level

independently associated ith hyponatremia

# In those in hom vasospasm developed, '%7 levelsincreased 0"J- ithin *J hours, and (("*- ithin ; days• '%7 level independently associated ith vasospasm

• Increase in '%7 did not precede vasospasm, but increasedconcurrently

# May be a good mar3er>"

# 7atients ith increasing '%7 levels after admission had%& CHA%G in their admit GCS after to ee3s

# 7atients ith no change, or decrease in '%7, had a ;point improvement in GCS * ee3s after admission

McGirt, ML CORRELATION OF SERUM RAIN NATRIURETIC !E!TI"E #IT$ $%!ONATREMIA AN" "ELA%E"ISC$EMIC NEUROLO&ICAL "EFICITS AFTER SUARAC$NOI" $EMORR$A&E, %eurosurgery Lune *44J


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Direct %eural :ects

• Generali@ed hyperactivity of thesympathetic nervous system occurs afterSAH# Sustained activity leads to a decrease in

plasma volume and blood volume

• Acute brain in5ury may lead to an

interruption in sympathetic o to 3idneys# Increases glomerular blood o, G!? and thusdiuresis

# Decreases renin release, and promotes

natriuresis


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Diagnosis

• 'ecause those patients at ris3 forCSW, are also at ris3 for SIADH, the

to must be distinguished>

CSW SIADH


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CSW SIADH

UHypovolemia

clinical dehydration lo CV7

Uuvolemia or

hypervolemia

%egative salt balance

Mar3edly elevatedna

Variable na

levated ithhypo%a

%ormal

Serum ADH and A%7 not helpful• $i3ely that SIADH and CSW, in the setting of headin5ury2surgery, represent to opposite ends of aspectrum=

• pts probably have both e-aggerated natriuresis and elevated

ADH release, and hich e:ect predominates depends on relativeintensities


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.reatment

• .reat underlying process

• Volume and sodium replacement

• %S, ;+ %aCl, or enteral salt for restoring%aCl balance# nteral salt preferable if euvolemia already

restored• Volume e-pansion can lead to increased aldosterone,

hich can then promote more %a loss• ?estore uvolemia

• !ludrocortisone# Wor3s on renal tubule to increase %a

renal siadh di csw

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