FEUNRMF

MEDICINE2017
INTERNAL MEDICINE - NEPHROLOGY
RAMON MORA, MD – 03/08/16
HYPONATREMIA by   the   oncotic   pressure,   is   allowed   to   pass   through   the  
-­‐  BODY  WATER  COMPOSITION     lymphatic  flow  so  that  we  don’t  have  edema  formation.  
-­‐ How   then   do   we   separate   the   fluid   or   the   water   from  
the  extracellular  and  the  intracellular?    

Suppose   this   is   a   70   kg   man,   if   you’re   going   to   If   the   force   governing   the   separation   of   intravascular  
compute  the  total  body  water  of  a  70  kg  man,  the  total  body   and   interstitial   is   brought   about   by   the   Starling   forces,   here  
water  is  60%,  (50%  for  females)  of  his  weight.  The  total  body   we  rely  on  the  osmolality.  Osmolality  is  the  concentration  of  
water  is  further  subdivided  into  ECF  (extracellular  fluid),  which   solute   particles   present   in   one   fluid   compartment,   and   they  
is  1/3  of  total  body  water,  and  ICF  (intracellular  fluid),  which  is   should   be   almost   equal   so   that   there   will   be   no   major  
about   2/3   of   the   total   body   water.   And   under   ECF   we   have   movement  of  water.    
+
intravascular  and  interstitial  fluid.    ISF  is  about  3/4  of  the  ECF   The  major  cation  in  the  ECF  is  Na  and  the  major  cation  
+
while  the  IVF  is  ¼  of  the  ECF   in  the  ICF  is  K  along  with  their  negatively  charged  ions.  They  
-­‐ So  how  do  we  control  the  movement  of  water  from  the   should   be   almost   equal   so   that   there   would   be   no   major  
interstitial  and  intravascular?   change.   The   boundary   that   divides   them   is   the   cell   membrane  
as   the   capillary   wall   divides   the   between   the   interstitial   and  
the  intravascular  bed.    
Serum  osmolality  is  what  we  measure  in  the  hospital  or  
in  the  clinics,  so  we  should  have  the  Na,  the  glucose  and  the  
BUN.    

If   glucose   is   written   or   reported   in   mg/dL   for   the  

conventional   unity,   we   have   to   divide   it   by   18.   If   BUN   is  
The   forces   governing   the   movement   of   fluid   from   the   reported  as  mg/dL,  we  need  to  divide  it  by  2.8.  If  the  report  
interstitial   and   intravascular   spaces   are   the   Starling   forces.   will   come   out   as   umol/L   we   don’t   have   to   divide   it   by   18   or  
Their  boundary  is  the  endothelial  layer  /  blood  vessel  wall  or   2.8  
+
capillary   wall.   At   the   end   of   the   arterial   line,   hydrostatic   The   major   determinant   of   the   osmolality   is   Na   so   that   if  
+
pressure   is   higher   than   the   oncotic   pressure,   the   high   there   is   low   Na   (less   than   135)   –   there   is   hypoosmolality,   and  
hydrostatic   pressure   pushes   the   plasma   water   out   from   the   as   a   consequence   of   hypoosmolality,   what   will   happen   next?  
+
vascular   bed,   so   as   the   plasma   water   goes   out,   the   protein   If   Na   is   low   in   this   compartment,   the   water   will   go  
remains   inside   the   lumen,   making   the   oncotic   pressure   intracellularly  because  it  is  more  concentrated  there  
intravascularly   increase.   As   it   increases,   it   starts   to   gather   the   And   this   is   what   is   happening;   if   there   is   hyponatremia,  
plasma  water  or  the  water  that  is  present  in  the  interstitium.   there  is  cellular  swelling.  This  is  the  initial  thing  that  is  going  
In   this   way,   we   can   prevent   edema   formation.   Whatever   on   in   our   brain   that’s   why   in   hyponatremia,   the   clinical  
excess   water   that   cannot   be   taken   out   from   the   interstitium   manifestations  are  neurologic  in  nature  because  they  develop  
cerebral  edema.  
 
Transcribed by: AYUYAO, GABASAN, DEMONYOTES
 -­‐ Vasopressin   always   included   because   when   you   have   has   been   transported.   The   peritubular   capillaries   lying   along  
hyponatremia,  almost  always,  vasopressin  is  involved.     the  sides  of  the  basolateral  membrane  are  continuation  of  the  
efferent  arterioles.  
Vasopressin   is   released   at   the   osmolality   of   280-­‐285  
mOsm   such   that   ADH/AVP   are   also   increased.   What   will  
happen  is  that  there  would  be  increasing  absorption  of  water  
from   the   collecting   tubules.   As   we   try   to   reabsorb   the   H2O,  
from   the   CT,   the   osmolality   of   the   urine   increases   because  
water   is   reabsorbed.   As   we   reabsorb   H2O,   the   tubular   fluid  
increases   in   osmolality   and   the   urine   volume   diminishes   and  
ADH  allows  AQP  channels  to  reabsorb  more  H2O.  So  what  do  
you  think  is  the  color  of  the  urine?    Yellow,  dark  yellow  

So   where   is   vasopressin   produced?   Vasopressin   is  

produced   in   the   hypothalamus   and   stored   in   the   posterior  
pituitary  gland.  What  are  the  effects  of  vasopressin?  One  of  
the   effects   of   vasopressin   is   on   the   vascular   smooth  
muscles—vasopressin   interacts   with   the   V1   receptor   of   the  
smooth  muscle  and  they  can  cause  vasoconstriction.  

-­‐  So   in   the   cell   membrane,   what   is   the   purpose   here   of  

the  Na/K  ATPase?  
+ +
It   allows   the   Na   to   remain   outside   and   it   keeps   the   K   in  
+ +
because   the   natural   territory   of   Na   is   extracellular   and   K   is  
intracellular  

 Vasopressin  is  a  pressor  hormone,  so  it  can  increase  BP  

and   at   the   same   time,   vasopressin   increases   water  
reabsorption   and   with   water   reabsorption   we   have   here   a   V2  
receptor.   V2   receptors   are   located   at   the   basolateral  
membrane   of   the   principal   cells   of   the   collecting   tubule.   So   -­‐ Percentage  Reabsorption  of  filtered  Na  and  Cl  along  the  
after   the   interaction   of   the   vasopressin   with   V2   receptors,   euvolemic  nephron    
there  would  be  series  of  events  and  there  will  be  activation  of   This  is  a  nephron,  nephron  is  made  up  of  a  glomeruli  and  
+
the   aquaporin2.   With   the   activation   of   the   AQP2,   they   will   a   series   of   tubules.   60%   of   the   filtered   Na   is   reabsorbed  
+
imbibe  water  from  the  tubular  lumen.   proximally  and  about  30%  of  the  filtered  Na  is  reabsorbed  at  
the  thick  ascending  limb.  About  7%  from  the  DCT  and  then  2-­‐
3%   in   the   cortical   collecting   duct,   outer   medullary   collecting  
duct   and   inner   medullary   collecting   duct   of   the   filtered   Na   is  
reabsorbed  

So  this  water  will  be  transported  transcellularly  and  will  

be   spilled   out   into   the   interstitium,   and   in   this   area,   there  
would  be  peritubular  capillaries  that  will  catch  the  water  that  
 
Transcribed by: AYUYAO, GABASAN, DEMONYOTES
 +
In   the   Thick   Ascending   limb,   Na   gets   reabsorbed  
through   the   Na/K/2Cl   and   this   is   the   transport   system   being  
limited  by  the  Loop  diuretics  (Furosemide).  

+ -­‐
In   the   Distal   Convoluted   Tubules,   we   have   the     Na /Cl  
Cotransport,    this  is  the  one  being  stopped  by  the    Thiazides.  
Is   there   any   diuretic   that   will   act   in   the   cotransport?  
Assignment  

-­‐ So  how  do  we  reabsorb  Na  proximally?  

Our  main  way  to  reabsorb  Na  proximally  is  through  the  
Na-­‐H   exchanger   located   at   the   luminal/apical   membrane.  
+ + 3-­‐
There  are  other  Na  transporters  like  Na /PO4 cotransporter,  
Na/glucose  cotransport,  Na/AA  co  transport.  
+
As   the   Na   increases   here   (inside   the   proximal   tubule),  
+
what   causes   the   Na   to   move   out?   The   Na/K   ATPase   will   be  
+
activated  so  that  the  Na  that  has  built  up  in  the  intracellular  
space   will   be   brought   out   and   be   transported   by   the   In  the  Principal  cells  of  the  Cortical-­‐collecting  duct,  here  
+
peritubular   capillaries   located   along   the   side   of   the   we   reabsorbed   Na   via   the   ENaC   (epithelial   Na   Channel).  
+
basolateral  membrane       Amiloride  blocks  this  ENaC.  So  as  we  reabsorb  Na ,  we  render  
-­‐ +
Take   note   also   that   majority   of   the   HCO3   gets   this   lumen   to   be   negative,   so   it   favors   secretion   of   K ,  
+ +
reabsorbed   at   the   proximal   tubule,   as   we   reabsorb   Na ,   we   secretion  of  H .  
+ + -­‐ -­‐
give   up   H ,   H   then   binds   with   HCO3   to   form   H2CO3   and   And   then   take   note   also   that   90%   of   the   HCO3   gets  
-­‐
through   carbonic   anhydrase   we   form   H2O   and   CO2.   CO2   is   reabsorbed  proximally,  those  HCO3  that  were  not  reabsorbed,  
+
freely   permeable,   so   it   enters   the   luminal   membrane   then   may   be   reabsorb   distally   through   this   mechanism.   As   H   is  
-­‐ + -­‐
binds  to  form  H2CO3  and  splits  to  form  HCO3  and  H  (orange   secreted,   some   of   the   HCO3   that   were   not   reabsorbed  
-­‐ +
box)   So   the   HCO3   can   be   transported   using   the   Na/HCO3   proximally   will   bind   or   will   meet   with   the   H   forming   H2CO3  
transporter   and   will   form   CO2   (via   Carbonic   Anhydrase)   and   will   be  
-­‐
  transported   to   the   lumen   to   form   HCO3 .   So   we   bring   in   the  
 
Transcribed by: AYUYAO, GABASAN, DEMONYOTES
 -­‐
HCO3   through   the   Cl/HCO3   exchanger.   Compared   to   the  
-­‐
proximal   one   where   the   HCO3   will   be   transported   via   the  
Na/HCO3  co-­‐transporter  
Take  note  also  that  the  principal  cell  comprise  about  65%  
of  the  collecting  duct  cells  and  about  35%  are  formed  by  the  
intercalated  cells  
+
§ Principal  cells  –  responsible  for  Na  secretion  
This   is   where   the   mineralocorticoid   receptors   are  
located;  the  basolateral  membrane  of  the  principal  cells,  and  
this  is  where  the  V2  receptors  are  located.  This  is  where  your  
Aldactone  (spironolactone)  works  
 
+
§ Intercalated  cells  –  responsible  for  H  secretion  
-­‐ What  is  the  effective  circulating  volume?  
 
In   the   first   illustration,   recall   that   TBW   is   divided   into   ICF  
DIFFERENCE BETWEEN and  ECF  and  if  ECF  is  low,  we  can  stimulate  the  following:  
OSMOREGULATION AND VOLUME RAAS.   What   happens   when   we   have   volume   depletion,  
REGULATION: dehydration,   and   BP   decreases?   JG   apparatus   can   be  
stimulated  to  release  renin.  What  stimulates  JG  apparatus  to  
release  renin?  
  Osmoregulation   Volume  regulation  
o Hypovolemia.  JG  is  stimulated  and  renin  is  formed  
What   is   being   Plasma   Effective   and   then   later   on,   Angiotensin   1,   Angiotensin   2,  
sensed?   osmolality   circulating  volume   and  aldosterone  will  subsequently  be  released.  
§ What   will   angiotensin   2   do?  
Sensors   Hypothalamic   Carotid  Sinus   VASOCONSTRICTION.   Therefore,   if   I   am  
osmoreceptors   Afferent  arteriole   volume  depleted  and  I  want  to  raise  my  BP,  I  
Atria   would   be   having   vasoconstriction.   However,  
vasoconstriction   may   not   be   enough   and   I  
Effectors   Antidiuretic   RAAS   +
may   need   the   aid   of   Na   reabsorption.   So   I  
hormone   SNS   have   both   vasoconstriction   and   Na  
+

Thirst     Natriuretic   reabsorption  to  replenish  the  low  ECF.  So  this  
peptides,   is  a  compensatory  mechanism  for  the  drop  in  
including   ANP   and   volume  and  BP.  
urodilatin   • So   urinary   Na
+  
decreases   because  
Pressure   aldosterone’s   action   is   to   reabsorb   Na .   So  
+

natriuresis   +  
when  you  reabsorb  Na and  you  brought  it  to  
ADH   the   ECF,   and   you   want   to   increase   your   BP,  
+
what  is  the  effect  on  the  urine?  Urine  Na  will  
What  is  affected   Water  excretion   Urinary   Na  
consequently  decrease.  
and   via   thirst,   excretion  
§ When   our   blood   volume   is   low,   and   our   BP   is  
water  intake  
low,   we   can   also   stimulate   ADH.   So   what  
-­‐ What  are  the  causes  of  Vasopressin  release?   happens?  We  will  reabsorb  H2O,  and  there  will  
o Hypovolemia  –  volume  depletion   be   vasoconstriction   through   V1   receptors.   It  
o Hyperosmolality     can   also   stimulate   the   sympathetic   nervous  
These   are   the   two   stimuli   for   Vasopressin   release:   system  and  cause  vasoconstriction,  increase  in  
hypovolemia   and   hyperosmolality.   So   osmoregulation   comes   heart  rate  and  pumping  action  of  the  heart—
into   the   picture.   With   volume   depletion   and   hyperosmolality   net  effect  is  to  increase  the  BP.  
we   can   now   stimulate   the   hypothalamus   to   release   o Carotid  Stimulation  –  if  you  have  Congestive  Heart  
vasopressin.  At  the  level  of  280-­‐285  mOsm,  we  can  stimulate   Failure,   what   happens?   There   is   diminished  
vasopressin   release   but   it   takes   more   than   285   mOsm   to   perfusion   to   vital   organs.   Why?   Because   there   is   a  
stimulate  thirst  centers.  This  means  that  when  vasopressin  is   diminished   cardiac   output.   If   there   is   a   diminished  
released,  there  would  be  H2O  conservation  but  if  this  is  unable   cardiac   output,   there   will   be   less   flow   passing  
to  correct  the  hyperosmolality  or  volume  depletion,  this  is  the   through  the  carotid  sinus  baroreceptors;  this  will  be  
only   time   in   which   thirst   would   take   effect   and   we   would   take   sensed   as   having   a   diminished   effective   circulating  
in  water  or  fluids.  So  what  is  the  end  effect?  H2O  excretion  will   volume,   so   if   this   is   sensed   as   having   a   diminished  
be  diminished  because  of  the  action  of  ADH  and  we  will  take   effective   circulating   volume,   the   CHF   patient   will  
in  fluids  to  correct  the  high  osmolality.   feel   dehydrated   or   that   he   is   volume   dehydrated  
  even  if  he  appears  edematous.  So  you  will  get  into  
 
Transcribed by: AYUYAO, GABASAN, DEMONYOTES
 thinking,   why   would   I   think   that   this   patient   is  
volume-­‐depleted   when   he   is   in   fact,   edematous?   So  
remember   that   this   patient   is   edematous   because  
his   compensatory   mechanism   is   overly   effective—
+
he  keeps  on  reabsorbing  H2O,  Na ,  and  expands  the  
ECV   resulting   to   edema.   So   this   is   a  
counterproductive   compensatory   mechanism   in  
conditions  like  CHF—the  patient  would  feel  volume  
depleted   so   his   body   will   keep   on   reabsorbing   salt  
and   H2O.   But   actually,   there   is   no   depletion—it’s  
just   that   the   H2O   is   not   at   the   right   ‘place’   (which  
should  be  in  the  interstitium).  At  the  same  time,  the  
heart  is  not  adequately  pumping  so  there  would  be  
decreased   perfusion   to   vital   organs   and   these  
compensatory   mechanisms   may   eventually   shut  
off.      
o On   the   other   hand,   if   you   take   in   too   much   salt,  
what   is   the   mechanism   to   prevent   persistent   -­‐ So   you   now   have   to   think   of   the   causes   of  
hypertension?   There   is   such   a   thing   as   pressure   hypovolemia—is  this  a  renal  or  extra-­‐renal  cause?  
+
natriuresis.   You   prevent   Na   reabsorption,   and    
+ +
increase  elimination  of  urine  Na .  So  what  happens   -­‐   Renal   losses  –  meaning  the  patient  has  high  urine  Na  loss  of  
+
when  you  keep  on  excreting  urine  Na ?  So  we  have   >20  mEq/L.  So  what  are  these  renal  losses?  
a   normal   capacity   to   do   this   but   this   can   be   o Excessive  diuretic  use  
mimicked   by   the   presence   of   a   diuretic   wherein   you   o Deficiency  in  aldosterone  
increase  the  urinary  Na   § In  effect,  there  is  no  Na  to  reabsorb  
    o Salt-­‐losing  deficiency  –  tubulointerstitial  diseases  
HOW DO WE DEVELOP § There  may  be  salt-­‐losing  nephropathy  
HYPONATREMIA o Bicabonaturia   –   can   be   seen   in   Renal   tubular   acidosis  
and  metabolic  alkalosis  
§ RTA  type  2  –  proximal  defect,  there  is  failure  in  
-­‐
HCO3  reabsorption  because  there  is  a  defect  in  
carbonic   anhydrase.   If   you   do   not   have   carbonic  
+
REMEMBER   THIS   FORMULA   –   plasma   Na   is   equals   to   anhydrase,   there   can   be   no   conversion   of   H2CO3  
+ +
exchangeable  Na  +  exchangeable  K  over  TBW.  So  if  I  have  a   to   CO2   and   H2O.   We   need   CO2   to   pass   through  
very   active   vasopressin   or   ADH,   I   will   reabsorb   more   water   the   membrane   to   be   reabsorbed   and   inside,   it  
-­‐
and  if  I  reabsorb  more  water  I  will  expand  my  TBW,  if  I  expand   can  be  converted  to  HCO .  
+
my  TBW,  naturally  my  plasma  Na  will  go  down  because  they   § We  can  also  have  metabolic  alkalosis  as  a  form  
are  inversely  related   of   the   body’s   ‘defense’   to   increase   elimination  
-­‐
o Numerator  and  plasma  Na  are  directly  proportional   of  HCO3  in  the  urine.  
So   when   you   have   a   hyponatremic   patient,   it   is   very   o Ketonuria  seen  in  uncontrolled  DM  
important   that   you   should   always   compute   for   the   serum   o Osmotic   Diuresis   –   the   use   of   mannitol   used   in   CNS  
osmolality,   this   is   automatic   when   you   are   suspecting   diseases  involving  increased  intracranial  pressure  
hyponatremia.   When   you   have   confirmed   the   initial   results,   § Cerebral  Salt  wasting  seen  in  brain  hemorrhage  
request  for  BUN  and  sugar  to  compute  serum  osmolality  and   because   in   our   damaged   brain   cells,   there   is  
correlate  with  the  PE,  see  if  the  patient  is  hypovolemic:   also  BNP.  
+  
o Low  BP   § If   Urine   Na <20,   we   can   see   this   in   vomiting,  
o Narrow  pulse   diarrhea—conditions   in   which   there   is  
o Dry  oral  mucosa   diminished   flow   of   blood   volume   and   plasma  
o Flat  neck  veins   water   in   intravascular   space.   This   will   be   sensed  
o Thready  pulse   that   there   is   diminished   ECFV   and   RAAS   will   be  
o Postural  hypotension  –  higher  BP  in  supine  than     activated   to   bring   Na   down   and   because   of  
+
  aldosterone,  urine  Na  will  decrease  
  -­‐ In   the   Euvolemia   arm,   the   causes   are   mainly   hormonal  
  like  ADH.  In  hormonal  causes  of  deficiency  of  hormones  
  that   can   cause   hyponatremia,   usually,   there   is   elevated  
  urine  Na.    
  -­‐ In  HYPERVOLEMIA—these  patients  are  very  edematous.  
An   example   is   Nephrotic   syndrome—there   is   diminished  
 
Transcribed by: AYUYAO, GABASAN, DEMONYOTES
 albumin   and   oncotic   pressure   is   also   low.   So   where   will   Osmolality   here   increases   and   water   reabsorption  
plasma   H2O   go?   They   will   go   out   and   remain   in   the   increases  contributing  to  the  increased  TBW  and  there  will  be  
interstitial   space   and   the   px   develops   edema.   Another   hyponatremia.     This   is   why   thiazides   cause   more  
example  is  cirrhosis—the  fluid  accumulation  is  composed   hyponatremia   because   they   do   not   inhibit   renal   concentrating  
of   plasma   water,   which   should   be   running   mechanism   because   there   is   inhibition   of   water   reabsorption  
intravascularly.   In   CHF,   there   is   diminished   CO,   then   in   this   which   this   is   the   concentrating   segment   because   the  
there  would  be  activation  of  carotid  sinus  baroreceptor,   medullary   interstitium   tonicity   is   maintained.   oop   diuretics  
so   you   can   stimulate   vasopressin,   renin,   angiotensin,   cause   less   hyponatremia   and   blunt   countercurrent   and  
aldosterone.   So   these   three   examples   have   increased   concentrating   mechanism.   When   you   block   TAL,   there   is   no  
aldosterone  resulting  to  decreased  urine  Na  and  edema   Na/K   here   so   you   cannot   reabsorb   water   and   therefore,   you  
(and   a   feeling   of   volume   depletion).   So   what   will   the   blunt   the   concentrating   mechanism.   In   thiazides,   there   is   no  
RAAS  do?   effect  in  the  increase  of  electrolytes  whereas  there  is  an  effect  
  with  furosemides.  This  area  must  remain  hyperosmolar  to  be  
HYPOVOLEMIC HYPONATREMIA able   to   reabsorb   H2O.   While   you   keep   on   reabsorbing   H2O,  
-­‐ Thiazides–   polydipsia,   diuretic   induced   volume   TBW   increases   and   this   causes   hyponatremia.   So   basically,  
depletion.  Do  not  inhibit  renal  concentrating  mechanism   when   you   have   hyponatremia,   you   are   referring   more   to  
-­‐ Loop   diuretics   –   less   cause   of   hyponatremia,   blunts   thiazides.   But   they   will   probably   not   ask   you   about   this  
countercurrent  and  concentrating  mechanism   hahaha    
-­‐ Nonreabsorbable/poorly   reabsorbed   solute   –   glucose,   EUVOLEMIC HYPONATREMIA
ketones,  bicarbonate  
-­‐ Cerebral   salt   wasting   (subarachnoid   hge,   traumatic  
brain  injury,  craniotomy,  encephalitis,  meningitis)  

Why   do   euvolemic   hyponatremic   patients   have   high  

+
Na ?   What   are   the   causes   of   euvolemic   hyponatremia?  
Glucocorticoid   deficiency,   SIADH,   hypothyroidism.   So   what  
actually   happens?   When   there   is   vasopressin   effect,   there  
would   be   more   H2O   accumulation   and   we   gain   weight  
So   between   the   two   diuretics   above,   what   causes   more   because   we   expand   the   TBW.   If   we   reach   about   2-­‐3   kg   of   H2O  
hyponatremia   is   Thiazide.   Thiazides   work   on   the   DCT.   It   is   gain,  there  will  be  stimulation  of  ANP.  The  ANP  release  from  
said  that  they  do  not  inhibit  renal  concentrating  mechanism.   the  atrium  will  favor  diuresis,  loss  of  salt  and  H2O  and  thus  we  
+ + -­‐ +
When   the   tubular   fluid   flows,   we   reabsorb   Na ,   K ,   and   Cl .   will   have   Na   of   >40mEq/L.   This   is   why   hormonal   causes   of  
When   we   bring   these   electrolytes   to   the   ECF,   what   will   hyponatremia   that   involves   ADH   are   results   of   this  
happen   to   the   osmolality   of   the   medullary   interstitium?   phenomenon.    
INCREASE.  So   there  is  a  running  tubular  fluid   there  and   when    
there   is   increased   medullary   interstitium   (pressure?)   here,   FEATURES OF SIADH
what   will   happen   to   the   H2O   present   in   the   CT?   It   will   be   -­‐ Hyponatremia  and  hypoosmolality  
reabsorbed.   This   is   the   natural   occurrence   in   countercurrent   -­‐ A   Uosm   that   is   inappropriately   high   (greater   100  
mechanism.     mosmol/kg)  
When   you   block   the   tall   ascending   limb   because   you   -­‐ A  urine  Na⁺  concentration  greater  than  40  meq/L,  unless  
have  loop  diuretics,  what  will  happen  to  the  osmolality?  It  will   the  patient  is  volume-­‐depleted  for  some  other  reason  
not  increase  because  you  already  blocked  the  electrolytes.  So   -­‐ Normovolemia  
what  will  happen  to  the  H2O  about  to  pass  here?  We  cannot   -­‐ Normal  renal,  adrenal,  and  thyroid  function  
reabsorb  it  because  the  osmolality  here  is  low.   -­‐ Normal  acid-­‐base  and  K⁺  balance  
Let  us  divide  it  into  cortical  and  medullary  portions  (red   You   must   know   the   reasons   why   SIADH   develops   in   an  
line).  Cortex  above,  medulla  below.    When  we  block  the  distal   individual.  They  have  both  hyponatremia  and  hypoosmolality.  
tubule,   the   Na/Cl   cannot   pass   through   the   cortical   portion.   Read   it   in   you   Harrison’s.   Why   is   there   hypoosmolality   of  
But  reabsorption  here  continues.   +
these   patients’   urine?   Which   hormone   causes   the   Na   to   be  

 
Transcribed by: AYUYAO, GABASAN, DEMONYOTES
>40?   ANP.   Know   that   they   are   also   normovolemic   and   you  
should  also  know  the  factors  that  must  be  causing  the  SIADH.  
 
ADRENAL INSUFFICIENCY
-­‐ ADH   is   an   important   ACTH   secretagogue   that   is  
cosecreted   with   the   corticotropin   releasing   hormone  
(CRH)  
-­‐ Cortisol  feeds  back  negatively  to  CRH  andADH  
-­‐ Cortisol  deficiencyà  increased  release  of  ADH  
Why   does   adrenal   insufficiency   occur?   Remember   that  
both  ACTH  and  CRH  come  from  the  hypothalamus,  and  CRH  
stimulates  ACTH,  ACTH  stimulates  the  release  of  cortisol  from  
the   adrenal   cortex,   cortisol   inhibits   the   ADH,   cortisol,   and   NEUROLOGIC ABNORMALITY
ACTH.   So   what   will   happen   if   you   do   not   have   cortisol?   There   o Plasma  Na+  concentration  below  125  meq/L  
will   be   no   inhibitory   effect   on   ADH   and   this   will   continue   to   –  nausea  and  malaise  
work.   So   ADH   activity   is   increased   in   glucocorticoid   o Between  115  and  120  meq/L  
deficiency,  that’s  why  they  have  hyponatremia.     –  headache,  lethargy,  and  obtundation  
o Plasma  Na+  concentration  less  than  110  to  
115  meq/L  
–  Seizures,  coma  
 
The   manifestations   of   hyponatremia   are   generally  
neurologic.   So   this   is   what   happens   in   our   brain:   when   we  
have   hyponatremia,   the   concentration   of   solute   particles   in  
the  brain  is  higher  than  the  ECF.  So  where  will  H2O  go?  It  will  
go   into   the   brain   cell   so   there   will   be   cerebral   edema.   We  
cannot   allow   cerebral   edema   to   go   on   further.   So   the   brain  
  has   the   ability   to   adapt.   The   solute   particles   causing   the  
HYPOTHYROIDISM attraction   of   H2O   in   the   brain   will   start   to   go   out.   The  
-­‐ Decreased  CO   electrolytes   will   go   out   and   osmolality   goes   down.   When   the  
-­‐ Decreased  GFR   brain   parenchyma   osmolality   occurs,   there   will   be   less  
In  hypothyroid  state,  there  is  diminished  CO.  This  will  be   attraction   of   water   and   less   edema   formation.  So  how  do  you  
sensed  by  the  carotid  baroreceptors  that  there  is  diminished   equate  this  in  the  clinics?  So  you  will  see  a  true  hyponatremic  
+
ECF   volume   so   there   will   be   ADH   stimulation   and   RAAS   patient   who   has   around   120-­‐125   Na   but   the   patient   is  
nd th
stimulation.   awake.   Probably,   this   patient   is   already   on   the   2 -­‐4   day   of  
  hyponatremia.   So   there   is   adjustment   such   that   within   24  
PSEUDOHYPONATREMIA hours,   the   brain   adaptation   already   occurs.   So   after   two   days,  
CAUSES  OF  PSEUDOHYPONATREMIA   you   will   wonder   that   although   the   patient   has   true  
-­‐ Low  plasma  Na  concentration  with  normal  Posm   hyponatremia   and   yet   he   is   conscious   and   coherent.   Initially,  
o Severe  hyperlipidemia   this   patient   has   neurologic   manifestation   but   because   of   the  
o Severe  hyperproteinemia   brain  adaptation,  he  becomes  awake  and  coherent  despite  a  
+
o  Post   transurethral   resection   of   prostate   or   low  Na .        
bladder   o SYMPTOMS  
-­‐ Low  plasma  Na  with  elevated  Posm  
o Hyperglycemia  
o Administration  of  Mannitol  
o Administration  of  IV  Ig  with  maltose  
I   want   to   highlight   here   the   importance   of  
hyperlipidemia   and   hyperproteinemia.   In   one   liter   of   plasma,  
93%  of  that  is  H2O.  Only  7%  of  that  volume  is  fat  and  protein.  
+
Na     resides   with   H2O.   In   cases   of   hyperlipidemia   and  
hyperproteinemia,   solid   portion   can   increase   and   the   H2O  
+
portion   decreases.   When   this   happens,   Na   is   also   decreased  
along  with  H2O  so  there  is  hyponatremia.    
 
 
 
 
Transcribed by: AYUYAO, GABASAN, DEMONYOTES
 MAJOR STEPS IN THE INITIAL beyond   8   mEq/day.   So   what   is   the   danger   when   we  
+
EVALUATION OF HYPONATREMIA rapidly  increase  Na ?  Osmotic  demyelination.    
CASE  
o Plasma  Osmolality  
o Low:  true  hyponatremia   HINDI  NAPICTURAN  CASE  L  
§ The  px  is  a  male  65  kg  so  multiply  by  0.6,  TBW  =  39  
o Normal   or   elevated:   pseudohyponatremia   or  
L.   Remember   that   our   aim   is   only   8   mEq/day.   We  
renal  failure  
can   actually   ‘peg’   8   there.   So,   135-­‐127   and   their  
o Urine  Osmolality  
difference  is  8.  So  39  x  8  is  312  so  if  I  were  to  give  
o  Less   than   100   mosmol/   kg:   primary   polydipsia   +
312,  I  can  expect  to  increase  my  Na  by  8  mEq.  So  if  
or  reset  osmostat  
you   know   your   IV   fluids   of   normal   saline   solution  
o Greater   than   100   mosmol/kg:   other   causes   of  
with  154  mEq.  I  can  probably  use  2  L  of  this  so  that  I  
true   hyponatremia   in   which   water   excretion   is  
can   have   308   mEq/day   which   is   close   enough   to  
impaired  
312.  
o Urine  Na  concentration  
FORMULAS  FOR  USE  IN  MANAGING  HYPONATREMIA  
§  <   30   meq/L   :   effective   circulating  
𝑖𝑛𝑓𝑢𝑠𝑎𝑡𝑒  𝑁𝑎 ! − 𝑠𝑒𝑟𝑢𝑚  𝑁𝑎 !
volume  depletion   𝐶ℎ𝑎𝑛𝑔𝑒  𝑖𝑛  𝑠𝑒𝑟𝑢𝑚  𝑁𝑎 ! =    
§ >   30   meq/L:   SIADH,   renal   failure,   reset   𝑡𝑜𝑡𝑎𝑙  𝑏𝑜𝑑𝑦  𝑤𝑎𝑡𝑒𝑟
+
osmotat,  diuretics,  vomiting   Estimate  the  effect  of  1  liter  of  any  infusate  on  serum  Na    
Horacio  J.  Adrogué,  M.D.,  and  Nicolaose.  Madias,  M.D.  Hyponatremia.  The  
  New  England  Journal  of  Medicine.  Volume  342  Number  21.  2000  
So   if   you   have   a   hyponatremic   patient,   you   have   to    
measure   the   osmolality.   If   it   is   low,   then   it   is   a   true   § I  personally  use  this  equation  in  the  clinics  because  
hyponatremic   patient,   remember   that   there   is   also   +
it’s  easier  to  reach  the  desired  Na .  
pseudohyponatremia.  This  is  done  even  at  the  ER.  If  it  is  less    
than   100,   it   means   that   there   is   high   H2O   content   in   the  
CHARATERISTICS OF INFUSATES
patient’s  urine  because  he  keeps  on  drinking.  So  what  level  do  
we   stimulate   vasopressin?   280-­‐285   mOsm.   But   in   true  
hyponat,   even   at   275,   there   is   already   vasopressin  
stimulation.  So  they  stimulate  ADH  and  reabsorb  H2O  earlier.  
If   the   urine   osmolality   is   >100,   it   is   probably   due   to   other  
causes   of   true   hyponatremia   in   which   H2O   excretion   is  
impaired.    
So   what   happens   in   true   hyponatremic   patients?   They  
keep   on   absorbing   H2O   and   naturally,   their   urine   will   be  
concentrated.  For  example,  a  patient  developed  diarrhea  but  
was  unable  to  take  in  fluids  so  there  will  be  dehydration  and  
the  urine  will  become  very  yellow  because  it  is  concentrated.  
When   they   take   my   urine   osmolality,   it   would   be   more   than  
100.    
+
If   I   measure   the   urine   Na   in   true   volume   depletion,   it  
would   be   low.   The   RAAS   is   activated   and   there   is   water   and  
+
Na    retention.    
OSMOTIC DEMYELINATION
  SYNDROME (ODS)
TREATMENT OF HYPONATREMIA o Overly  rapid  correction  of  hyponatremia  (>8–10  mM  
in  24  h  or  18  mM  in  48  h)  
𝑆𝑜𝑑𝑖𝑢𝑚  𝑑𝑒𝑓𝑖𝑐𝑖𝑡
= 𝑇𝑜𝑡𝑎𝑙  𝑏𝑜𝑑𝑦  𝑤𝑎𝑡𝑒𝑟   𝑇𝐵𝑊 𝑥 𝑑𝑒𝑠𝑖𝑟𝑒𝑑  𝑆!" − 𝑎𝑐𝑡𝑢𝑎𝑙  𝑆!"   o lesions  of  ODS  classically  affect  the  pons  
  o para-­‐   or   quadraparesis,   dysphagia,   dysarthria,  
àTBW   is   estimated   as   lean   body   weight   times   0.5   for   diplopia,  and/or  loss  of  consciousness  
women  and  0.6  for  men  
 
RATE  OF  CORRECTION  
o 8-­‐10  meqs  per  24  hours  
o Not  >18  meqs  in  48  hours  
 
+
§ To  compute  for  the  Na  deficit,  you  have  to  note  if  
your   px   is   male   or   female.   If   female,   use   0.5.   So   if  
the  female  px  is  70  kg,  multiply  it  by  0.5  so  TBW  is  
35  L.  If  it’s  a  male  px  then  multiply  by  0.6  so  42  L.  So  
+
when   you   are   increasing   the   Na ,   you   should   not   go  
 
Transcribed by: AYUYAO, GABASAN, DEMONYOTES