This document discusses hyponatremia (low sodium levels in blood). It begins by defining hyponatremia as a sodium level below 135 meq/L. It then describes the causes and symptoms of hyponatremia, which can include headache, vomiting, seizures and coma depending on severity. The document categorizes hyponatremia based on plasma osmolality as hypertonic, isotonic or hypotonic. It discusses the various types in more detail including hypovolemic, euvolemic and hypervolemic causes. Treatment depends on the specific cause but may include saline solution, fluid restriction, or vasopressin receptor antagonists. The document emphasizes correcting sodium

1. A New Perspective onA New Perspective on
HyponatremiaHyponatremia
by Steve Chenby Steve Chen
Director of Nephrology,
Shin-Chu Branch of Taipei Veterans General Hospital

2. SodiumSodium
Reference Range:
136 – 145 meq/L

3. SodiumSodium
Hyponatremia is Na+
< 135 meq/L

5. ELECTROLYTEELECTROLYTE
DISORDERSDISORDERS
 Serum NaSerum Na++
< 135 meq/L< 135 meq/L
– Symptoms due to brain edema:Symptoms due to brain edema:
headache & vomiting ifheadache & vomiting if NaNa++
< 120< 120
meq/Lmeq/L
– CNS symptoms:CNS symptoms:
convulsions ifconvulsions if NaNa++
< 113 meq/L< 113 meq/L
– CV symptoms:CV symptoms:
CV collapse ifCV collapse if Na < 100 meq/LNa < 100 meq/L
Hyponatremia

6. HyponatremiaHyponatremia
Causes an osmotic fluid shift from
plasma into brain cells

7. Hyponatremic encephalopathyHyponatremic encephalopathy
 Hospital acquired:
SIADH
Post-operative state: 3-4 L hypotonic fluid
in 2 days in female  fatal
Encephalitis in children: fatal
 Risk factors:
Children : non-osmotic stimuli of ADH
↑brain/intracranial volume
Female: sex steroid inhibit
brain adaptation Hypoxemia

8. Hyponatremic encephalopathyHyponatremic encephalopathy
Outpatient :
Medications
Psychogenic polydipsia
Water
intoxification in infants
Marathon runners
Hip fracture
S/P colonoscopy : ADH↑from
bowel manipulation + polyethelene glycol for bowel preparation
Recreational drug:

9. ELECTROLYTEELECTROLYTE
DISORDERSDISORDERS
 Pathophysiology: CNSPathophysiology: CNS
– Water shifts into brain cellsWater shifts into brain cells
– ApathyApathy –– Altered ConsciousnessAltered Consciousness
– AgitationAgitation –– ConvulsionsConvulsions
– HeadacheHeadache –– ComaComa
– Risk of brain damage > during treatmentRisk of brain damage > during treatment
– Cerebral demyelination syndrome(CDS)Cerebral demyelination syndrome(CDS)
Hyponatremia

10. Cerebral Demylination SyndromeCerebral Demylination Syndrome
CDSCDS
risk factorsrisk factors
 Development of Hypernatremia
 ↑S-Na > 25 meq /L in 48Hrs
 Hypoxemia
 Hypokalemia
 Mal-nutrition
 Severe liver disease
 Alcoholism
 Severe burns
 Cancer
 U osm ≤ 150 Kg/L

12. ELECTROLYTEELECTROLYTE
DISORDERSDISORDERS
 Serum OsmolalitySerum Osmolality
– Number of osmoles (osmotically activeNumber of osmoles (osmotically active
particles) in the serumparticles) in the serum
– Normal rangeNormal range
 275 to 295 mosm/L275 to 295 mosm/L
Fluid Balance
2[Serum Na+
] + ------------ + ------------
Glucose BUN
18 2.8

13. ELECTROLYTE DISORDERSELECTROLYTE DISORDERS
HyponatremiaHyponatremia
Flow of D.D.Flow of D.D.
Plasma
Osmolality
Normal (275-295)
Isotonic
hyponatremia
Low (< 275)
Hypotonic
hyponatremia
High (> 295)
Hypertonic
hyponatremia
Hypovolemic Hypervolemic Euvolemic

14. ELECTROLYTEELECTROLYTE
DISORDERSDISORDERS
 HypertonicHypertonic HyponatremiaHyponatremia (P(Posmosm > 295)> 295)
– Large quantities of solute in ECFLarge quantities of solute in ECF
– Water moves from ICF ECFWater moves from ICF ECF
– HyperglycemiaHyperglycemia most common causemost common cause
 Each 100 mg/dl plasma glucose will serumEach 100 mg/dl plasma glucose will serum
NaNa++
by 1.6 meq/Lby 1.6 meq/L
– TreatmentTreatment
 Volume replacementVolume replacement
Hyponatremia, hypertonic

15. ELECTROLYTEELECTROLYTE
DISORDERSDISORDERS
 IsotonicIsotonic HyponatremiaHyponatremia (P(Posmosm 275 - 295)275 - 295)
– ““PseudohyponatremiaPseudohyponatremia””
– Artifact in serum NaArtifact in serum Na++
measurementmeasurement
 2° High levels of plasma proteins and lipids2° High levels of plasma proteins and lipids
– Etiology:Etiology:
 HyperlipidemiaHyperlipidemia
 HyperproteinemiaHyperproteinemia
Hyponatremia, isotonic

16. ELECTROLYTEELECTROLYTE
DISORDERSDISORDERS
 HypotonicHypotonic HyponatremiaHyponatremia (P(Posmosm < 275)< 275)
Plasma Osmolality
Normal (275-295)
Isotonic
hyponatremia
Low (< 275)
Hypotonic
hyponatremia
High (> 295)
Hypertonic
hyponatremia
Hypovolemic Hypervolemic Euvolemic
Hyponatremia, hypotonic

18. ELECTROLYTEELECTROLYTE
DISORDERSDISORDERS
 HypovolemicHypovolemic HyponatremiaHyponatremia
– RenalRenal NaNa++
lossloss
 Urine NaUrine Na++
> 20 meq/L> 20 meq/L
 Etiology:Etiology:
– Diuretic useDiuretic use
– Salt-wasting nephropathy (renal tubular acidosis, chronicSalt-wasting nephropathy (renal tubular acidosis, chronic
renal failure, interstitial nephritis)renal failure, interstitial nephritis)
– Osmotic diuresis (glucose, urea, mannitol,Osmotic diuresis (glucose, urea, mannitol,
hyperproteinemiahyperproteinemia
– Mineralocorticoid (aldosterone) deficiencyMineralocorticoid (aldosterone) deficiency

19. ELECTROLYTEELECTROLYTE
DISORDERSDISORDERS
 HypovolemicHypovolemic HyponatremiaHyponatremia
– ExtrarenalExtrarenal NaNa++
lossloss
 Urine NaUrine Na++
< 20 meq/L< 20 meq/L
 Etiology:Etiology:
– Volume replacement with hypotonic fluidsVolume replacement with hypotonic fluids
– GI loss (vomiting, diarrhea, fistula, tube suction)GI loss (vomiting, diarrhea, fistula, tube suction)
– Third-space loss (burns, hemorrhagic pancreatitis,Third-space loss (burns, hemorrhagic pancreatitis,
peritonitis)peritonitis)
– Sweating (cystic fibrosis)Sweating (cystic fibrosis)

20. ELECTROLYTEELECTROLYTE
DISORDERSDISORDERS
 HypovolemicHypovolemic HyponatremiaHyponatremia
– TreatmentTreatment
 Re-expansion of ECF withRe-expansion of ECF with isotonic salineisotonic saline
 Correction of underlying disorderCorrection of underlying disorder

21. To calculate Na deficitTo calculate Na deficit
Sodium deficit = total body water X
(desired Na - present Na)
TBW = body wt x 0.6 males
0.5 females

22. Sodium DeficitSodium Deficit
 Na deficit= Vd of plasma Na x Na deficit per liter﹝ ﹞
 Vd of plasma Na = TBWa = 0.5 x LBW if﹝ ﹞
female =0.6 x LBW if man
 60Kg woman, Thiazide 5 days, acute confusion,
plasma Na = 108meq/L. If Na =120 is safe,﹝ ﹞ ﹝ ﹞
sodium deficit= 0.5x 60x﹙120-108 =360﹚
 Urine Na> 40meq/L indicates Normovolemia
restored
 NS supplied for fear of postsupply overdiuresis

23. Post-N/S diuresis: turn off ADHPost-N/S diuresis: turn off ADH
U osm <100 mOsm
Initial rate before P-Na targeted:
ongoing free
water loss =
UV x [ 1-( UNa+UK / PNa+PK ) ]
Later rate after P-Na targeted:
free
water loss
= UV x [ 1-( UNa+UK-oral Na+K-IV

25. ELECTROLYTEELECTROLYTE
DISORDERSDISORDERS
 EuvolemicEuvolemic Hyponatremia(1)Hyponatremia(1)
– SIADHSIADH
 Hypotonic hyponatremiaHypotonic hyponatremia
 Inappropriately elevated urine osmolality (usually > 200Inappropriately elevated urine osmolality (usually > 200
mosm/kg)mosm/kg)
 Elevated urine NaElevated urine Na++
(> 20 meq/L)(> 20 meq/L)
 Clinical euvolemiaClinical euvolemia
 Normal adrenal, renal, cardiac, hepatic, and thyroid functionNormal adrenal, renal, cardiac, hepatic, and thyroid function

26. ELECTROLYTEELECTROLYTE
DISORDERSDISORDERS
 EuvolemicEuvolemic Hyponatremia(2)Hyponatremia(2)
– Etiology:Etiology:
 HypothyroidismHypothyroidism
 Pain, stress, nausea, psychosis (stimulates ADH)Pain, stress, nausea, psychosis (stimulates ADH)
 Drugs: ADH, nicotine, sulfonylureas, morphine,Drugs: ADH, nicotine, sulfonylureas, morphine,
barbs, NSAIDS, APAP, Carbamazepine,barbs, NSAIDS, APAP, Carbamazepine,
Phenothiazines, TCAs, Colchicine, Clofibrate,Phenothiazines, TCAs, Colchicine, Clofibrate,
Cyclophosphamide, Isoproterenol, Tolbutamide,Cyclophosphamide, Isoproterenol, Tolbutamide,
MAOIsMAOIs

27. ELECTROLYTEELECTROLYTE
DISORDERSDISORDERS
 EuvolemicEuvolemic Hyponatremia(3)Hyponatremia(3)
– Etiology:Etiology:
 Water intoxication (psychogenic polydipsia)Water intoxication (psychogenic polydipsia)
 Glucocorticoid deficiencyGlucocorticoid deficiency
 Positive pressure ventilationPositive pressure ventilation
 PorphyriaPorphyria
 Essential (reset osmostat orEssential (reset osmostat or sick cell syndromesick cell syndrome))

28. ELECTROLYTEELECTROLYTE
DISORDERSDISORDERS
 Treatment of Severe Hyponatremia(4)Treatment of Severe Hyponatremia(4)
– Indications:Indications:
 Serum NaSerum Na++
< 120 meq/L< 120 meq/L
 Rapid development ( NaRapid development ( Na++
> 0.5 meq/L/hr)> 0.5 meq/L/hr)
 Patient in extremis (coma, seizures)Patient in extremis (coma, seizures)
– 3% Saline Solution (513 meq/L) @3% Saline Solution (513 meq/L) @ 25 - 10025 - 100
ml/hrml/hr
 NaNa++
should not exceed 0.5 – 1.0 meq/L/hrshould not exceed 0.5 – 1.0 meq/L/hr

29. Time Classification of SIADH-Time Classification of SIADH-
HyponatremiaHyponatremia
Duration Clinical
setting
Risk Therapy
Acute <48Hr Post-
operative
Brain cell
swelling
↑﹝Na by up﹞
to 5meq/L/H
Chronic Unknown
Or > 48Hr
Many Cerebral
demyelination
syndrome
↑﹝Na﹞
<0.33meq/L/
H

30. Therapy for SIADHTherapy for SIADH
 Aggressive Tx only for Pts with coma/seizure:
↑ Na up to 5meq/L to control CNS S/S; then﹝ ﹞
↑ Na 8meq/L/D﹝ ﹞≦
 Slow correction when brain cell size normal
↑ Na 8meq/L/D to prevent CDS﹝ ﹞≦ 3%
NaCl 1cc/Kg/Hr= ↑ Na 1meq/L/Hr﹝ ﹞
 Even slower correction if manutrition or
hypercatabolic state(poor availability of K or
organic osmoles

31. SIADH with chronic hyponatremiaSIADH with chronic hyponatremia
A 50Kg,SIADH due to tumor, plasma
Na 120meq/L, asymptomatic﹝ ﹞
TBW=30L; ICF 20L
Total ICF osmoles normally=20x2x140=5600
If ICF osmoles unchanged,
ICF=5600/2x120=23.2L
Time(hr)=140-120/0.5=40Hr
 Therapeutic goal: To lose 3L of EFW within 40Hr

32. Treatment guidelinesTreatment guidelines
Administration of oral or IV Na+
(3%)
Supplements
Encourage foods high in Na+
Fluid restriction
Monitor Neurological Status
Normovolemic hyponatremia:V2 antagonist
– Vaprisol (conivaptan) – IV infusion
– Samsca (tolvaptan) - PO

34. Renal water channels: AQPRenal water channels: AQP
 Aquaporins: AQP 0 ～ 12
 AQP 0: Cataract
 AQP 1 in proximal & thin descending LOH:
re-absorption of most filtered fluid= partial
NDI
 AQP 2 in apical of collecting duct: urine
concentration= NDI
 AQP 3 & 4 in baso-lateral of collecting duct:
 AQP 5: SS
 AQP 7 in apical of S3 proximal: 10% as
water route; glycerol re-absorption
 AQP 11 in intracellular vesicles: PCKD
Sei Sasaki: Tokyo Medical and Dental

35. AQP 2 binding protein complexAQP 2 binding protein complex
Trafficking of AQP2
Mis-routing to baso-lateral membrane
instead of apical
SPA-1: a GTP-ase activating protein for
Rap1
Cytoskeleton protein actin
Sei Sasaki: Tokyo Medical and Dental
University

36. Urinary concentration modulationUrinary concentration modulation
↑
c AMP
AQP2 trafficking
and expression

37. Post-3%N/S free water diuresisPost-3%N/S free water diuresis
 Psychogenic polydipsia
 DC of DDAVP
 Water intoxification in infants
 Hypotonic fluid plus DDAVP for
overcorrection of hyponatremia
 Case:
70Kg, TBW 35, S-Na 110meq/L
1L 3% NaCl  11.2 meq/L↑
by closed system equation
 22
meq/L if 3L free water diuresis

38. Post-3%N/S natriuresisPost-3%N/S natriuresis
SIADH
Cerebral salt wasting
Case:
SIADH with fixed urine osmolality
600 1L 3% NaCl  11 meq/L ↑
by a closed system
equation
 7 meq/L ↑ if 1L urine Na+K
=250 meq/L

40. ELECTROLYTEELECTROLYTE
DISORDERSDISORDERS
 HypervolemicHypervolemic Hyponatremia(1)Hyponatremia(1)
– Without advanced renal insufficiencyWithout advanced renal insufficiency
 Urine NaUrine Na++
< 20 meq/L< 20 meq/L
 Cirrhosis, ascites, CHF, Nephrotic syndromeCirrhosis, ascites, CHF, Nephrotic syndrome
– Advanced acute or chronic renal insufficiencyAdvanced acute or chronic renal insufficiency
 Urine NaUrine Na++
> 20 meq/L> 20 meq/L
 Renal failure (inability to excrete free water)Renal failure (inability to excrete free water)

41. ELECTROLYTEELECTROLYTE
DISORDERSDISORDERS
 HypervolemicHypervolemic Hyponatremi(2)Hyponatremi(2)
– TreatmentTreatment
 Optimize treatment for underlying disorderOptimize treatment for underlying disorder
 Judicious salt and water restrictionJudicious salt and water restriction
 ++ DiureticsDiuretics
 ++ DialysisDialysis

43. Hypouricemia in hyponatremiaHypouricemia in hyponatremia
volume mechanism Reference
SIADH N/↑ water↑
Thiazide-induced
hyponatremia
↑/↓ water↑ Fichman et al,
AJM 1971
Polydipsia-induced
hyponatremia
↑ water↑ Hanihara et
al, JCP 58,
256-260, 1997
CSW ↓ ANF
→Proximal tubule
Maesaka et al,
CN 33, 1990
Hyperbilirubinemia
severe
↓ Cholaemia
→ Proximal tubule
Tinatul et al,
JMAT 1970

44. Trickle-down hyponatremiaTrickle-down hyponatremia
Oh et al, JASN 8: 108A, 1997Oh et al, JASN 8: 108A, 1997
subgroups ↓Solutes ↓ADH Reference
I. Tea/Toast
potomania
Toast: ↓
Protein;
Thiazide for
HTN: ↓Nacl
Tea:
electrolyte-
free water
Boulanger et al,
NDT 14: 2714-
15, 1999
II. Slim
potomania
Low protein
intake/NaCl;
Exercise
↑Water Thaler et al,
AJKD 31:
1028-31, 1998
III. Beer
potomania
↑CHO+fat+a
lcohol;
↓Protein+
NaCl
↑Water Oh et al,
1997

45. Beer PotomaniaBeer Potomania
 cH2O= Solute excretion/ Uosm﹙1-Uosm/
Posm﹚
 Dependence of water clearance on daily
solute excretion at low urine osmolality(<100)
 Uosm=80mOsm/kg(<100)
solute 300mOsm; cH2O=2.7L;
solute 600, cH2O=5.4;
solute 900, cH2O=8.1L
 Total solute excretion = urea + 2x﹙Na+K﹚
urea= 50x7+100 ～ 150=450( for 70g
protein intake)
Thaler et al, AJKD 1998

46. Basal water channels(BWC)Basal water channels(BWC)
 Vasopressin-independent water permeability
high in the inner MCD
Lankford et al, AJP 261: 554-566, 1991
 Hereditary DI in rat
Edwards et al, AJP 239: 84-91, 1980
 A different AQP: severe impaired urinary
concentrating ability in transgenic mice
lacking AQP1 water channels
Ma et al, JBC 273:4296-99,1998
 Predominant in the neonatal stage :
physiological DI in water
load≧20ml/Kg→water diuresis
 Chlopropamide↑

47. BWC>>AQP2BWC>>AQP2
Halperin et al, Clinical Nephrology 56: 339-345, 2001Halperin et al, Clinical Nephrology 56: 339-345, 2001
 In the neonatal stage
 Trickle-down hyponatremia:
Low volume delivery to MCD
low GRF/↑ re-absorption of filtrate in proximal tubule
↑water permeability in cortical distal nephron
low solute excretion rate: Urea+NaCl
low protein diet (low urea)
low NaCl intake ± large non-renal or prior renal NaCl loss
ADH suppression

49. The Janus effect: 2 faces ofThe Janus effect: 2 faces of
AldosteroneAldosterone
Chronic L-NAME

50. Sodium Channel: ENaCSodium Channel: ENaC
Modes of ENaC regulationModes of ENaC regulation

51. Aldosterone/Vasopressin in CDAldosterone/Vasopressin in CD
E Na C Na K ATP ase
Na
K
V2R
Aquaporin
H2O
MR
ATP
c AMP
PKA
Nedd4-2
Aldosterone
Sgk
Nedd4-2: neural precursor cell expressed developmentally down-regulated 4-2
Sgk: serum and glucocorticoid inducible kinase

52. Aldosterone/Vasopressin/CaSRAldosterone/Vasopressin/CaSR
in CDin CD
E Na C
ROMK
Na K ATP ase
Depolarize
+
Aldosterone
+
Na
K
V2R
Aquaporin
H2O
CaSR
CaSR

53. Angiotensin II in CNT and CCDAngiotensin II in CNT and CCD
E Na C
ROMK1
Na K ATP ase
Na
K Protein
tyrosine
kinase(c-
Src)
V2R
AT1R
A candidate for an aldosterone-independent mediator of K preservation
during volume depletion

54. Clinical correlation of ENaCClinical correlation of ENaC
Vivek Bhalla et al: JASN 19: 1845-54,2008

55. Processing of natriuretic peptideProcessing of natriuretic peptide
ConvertaseSignal peptidase

56. Corin: new insights into ANPCorin: new insights into ANP
Corin: a transmembrane serine protease
identified in the heart
Convert pro-ANP to active ANP
Lack of corin →
Salt sensitive HTN in mice
Single nucleotide polymorphism→
African Americans with HTN and cardiac
hypertrophy Q Wu et al: KI 75: 142-146, 2009

57. Mutations of renal Na channelsMutations of renal Na channels
 Liddle syndrome: β and γ subunits of amiloride-sensitive
ENaC
 Gordon syndrome: WNK1 and WNK4 kinases
 Glucocorticoid remediable aldosteronism: aldosterone
synthase/11 β hydroxylase
 Adrenal hyperplasia: 11α hydroxylase/β hydroxylase
 Apparent mineralocorticoid excess: mineralocorticoid
receptor, 11 βhydroxystreoid dehydrogenase
 Progersterone induced hypertension: mineralocorticoid
receptor
 Psuedo-hypoaldosteronism (PHA)

58. PseudoHypoAldosteronism: PHAPseudoHypoAldosteronism: PHA
Bonny et al, JASN 13: 2399-2414, 2002Bonny et al, JASN 13: 2399-2414, 2002
Clinical Gene Defects
Type I: AR
AD
Renal: salt wasting/hypo-Na
Hyper-K
Metabolic acidosis
PAC↑/PRA↑
Extra-renal: chest, GI, skin
Renal : spontaneous remission
ENaC
Mineracorticoid receptor
Type II: AD
( Gordon syndrome )
Renal: HTN, salt sensitive
Hyper-K
HCMA
normal PAC; PRA↓
A: 1q31-q42
B: WNK4
C: WNK1
Type III:
Acquired
(obstructive
nephropathy; UTI;
lead; amyloidosis)
GFR↓; Excessive salt loss
Hyper-K
HCMA
PAC↑/PRA↑
Transient PHA

59. Salt transport in DCTSalt transport in DCT
TSC
Na
2Cl
V2R
Inactive
TSC dimer TSC
monomer
AT1R
MR
SPAK

60. PHA-2: WNK1&4/SPAK/TSCPHA-2: WNK1&4/SPAK/TSC
(gain)(gain)
TSC
Na
2Cl
Inactive
TSC dimer TSC
monomer
SPAK
4
1
Sei Sasaki: Tokyo Medical and Dental University

61. Chloride channel: CLCChloride channel: CLC
hCLC-Ka
(rCLC-K1)
hCLC-Kb
(rCLC-K2)
CLC-5
Location TALH,
basolateral
TALH, DCT,
αIC basolateral
PCT, αIC
intracelluar
shunt by H
ATPase
Disease NDI, DDAVP-
insensitive
(Clcnk1)
Tyep III Bartter
syndrome
(CLCNKB)
Mixed Bartter-
Gitelman
(CLCNKB)
XLR
nephrolithiasis
(Dent’s: CLC-5)
↓Receptor-
mediated
endocytosis

62. Variants of Bartter’s syndromeVariants of Bartter’s syndrome
Israel Zelikovic, NDT 18: 1696-1700, 2003Israel Zelikovic, NDT 18: 1696-1700, 2003
Defective
transporter/protein
Clinical Locus
Type I NKCC2 (TAL) Antenatal 15q
Type II ROMK (TAL/CD) Antenatal 11q
Type III ClC-Kb (TAL,DCT) Classic 1p36
Type IV Barttin (β of CIC-
Ka/CIC-Kb)
BSND
(Deafness)
1p31
AD
Hypercalciuria
CaSR
(PT/TAL/DCT/CD)
Hypocalcemia 3q

63. Bartter’s syndrome in THALBartter’s syndrome in THAL
NKCC
ROMK
Na K ATP ase
Ca, Mg pH
Na/K
K
2Cl
CaSR
Negative
Positive
ClC-Kb
2
1
3

64. Bartter with Sensori-NeuralBartter with Sensori-Neural
DeafnessDeafness
BSND
Barttin forms heterodimers
with ClC-Ka in thin ALH
with ClC-Kb in thick
ALH→ NDI
with ClC-K in marginal cells of stria
vascularis (inner ear) & vestibular dark cells

66. Gitelman’s / Bartter’s syndromeGitelman’s / Bartter’s syndrome
Gitelman’s Bartter’s
Molecular level ↓TSC in DCT ↓NKCC, ROMK, or
Cl
Age at onset Teenage Children
Clinical Tetany Failure to thrive
Mimicked by Thiazides Loop diuretics
Plasma Mg ↓ ↓
D.D. Hypocalciuria Hypercalciuria
Uosm ↓

67. Thiazide-induced hyponatremiaThiazide-induced hyponatremia
Renal salt wasting: via TSC in DCT
Water retention:
hypovolemia-induced ADH release
direct effect of ↑distal water reabsorption
( via PGE2↓; indomethacin↑)
Magaldi et al, NDT 15: 1903-5, 2000
↑thirst and water intake
No calcium wasting

68. Salt transport in DCTSalt transport in DCT
TSC
Na
2Cl
V2R
Inactive
TSC dimer TSC
monomer
AT1R
MR
SPAK

69. Vasopressin/CaSR in DCTVasopressin/CaSR in DCT
TSC
TRPV5
Na K ATP ase
pH pH
Na
Ca
2Cl
CaSR
Positive
PositiveCaSR
CaATPase
NCX
V2R
Kinase
SPAK

71. Salt-losing nephropathySalt-losing nephropathy
Salt-losing nephropathy with
inappropriate secretion of ANP( 10 ～
47fmol/ml): no cardiac or cerebral
abnormality pseudo-bartter
syndrome: concentaring power highly-conserved;
normokalemic metabolic alkalosis; no response
to indomethacin therapy
 Granulomatous interstitial nephritis&uveitis:
non-caseating granuloma
6-M steroid therapy
Primary renal candidiasis:
caseating renal granuloma→medullary destruction

72. Milk alkali syndromeMilk alkali syndrome
↑Free P-Ca++ /Mg++
CaCO3 in duodenum + ferment H+
→ Free Ca++ in lumen;
if low HPO4 in GI (poor intake)
→ Free P-Ca++ ↑ via para-
cellular route
Hypercalcemia GFR↓

73. Anorexia nervosa + AntacidsAnorexia nervosa + Antacids
Mitchell Lewis HalperinMitchell Lewis Halperin
P-Na=118mM ; U-Na 44mM
pH=7.2; P-HCO3=9
P-K=2.0mM; U-K=17mM
K deficit >120
P-Ca 2.56mM; P-alb 2.7g/dl
UV>6L; Uosm=150
P-Mg 1.5mM

75. Shaded areas refer to changes in total body sodium because of
differences in intake and excretion

76. ‘skin Na+
storage’
Macrophages act as local osmo-sensors
Weekly (circaseptan) patterns in sodium excretion:
inversely related to aldosterone and directly to cortisol.
TBNa : monthly (infradian) rhythms independent of
extracellular water, body weight, or blood pressure
nstead exhibited far longer ( monthly) infradian rhythms independent of ext
instead exhibited far longer ( monthly) infradian rhythms independent of ex

77. 23
Na-magnetic resonance imaging (MRI) can measure sodium in the
skin and muscle at the calf: despite remarkable reduction in tissue Na+
content, no change in body weight was observed