sodium and water metabolism

1. ELECTROLYTES:
SODIUM METABOLISM
Dr. Md Aftab Alam
3rd Year PGT, General medicine
NRSMCH

2. SODIUM AND WATER
• Water is the most abundant constituents of body , comprising 50% of
body weight in women and 60% in men
• Total Body water is distributed into two major compartments; 55-75%
is intracellular(ICF) and 25-45% is extracellular(ECF)……ECF is further
subdivided in intravascular(Plasma) and extravascular(interstitial)
space in ratio 1:3
• Sodium is the most abundant ion of extracellular compartment and is
the primary determinant of osmolality of ECF
• Normal plasma level of Na+ is 135-145 mEq/L
• Normal plasma osmolality is 275-295 mOsm/kg

3. IONIC COMPOSITION OF DIFFERENT FLUID
COMPARTMENTS

4. PHYSIOLOGY
• OSMOLARITY: It is no of osmoles per litre of solution . Affected by
volume of various solutes and temperature of solution
• OSMOLALITY: It is no of osmoles per kg of solvent and is independent
of temperature or solutes
• Effective solute are impermeable to cell membrane ,i.e Na, mannitol
and contribute to osmolality of the compartment it is in
• Ineffective solute are freely permeable to cell membrane ,..urea ,
ethanol
• Glucose is ineffective solute in physiological state but in high conc it
becomes effective solutes
• Osmolality of plasma = 2[Na+] + [Glucose]/18 + [ BUN ]/2.8

5. SODIUM METABOLISM
• normal plasma level is 135-145 mEq/L
• Sodium intake- normal Indian diet contains 11g per day which is more
than WHO recommendation of 5g per day
• Functions of sodium
i. Sodium and its attendant anions(Cl and HCO3) account for 90_95% of
osmotic pressure in ECF
ii. It determines membrane potential and neuromuscular excitability
iii. Acid base balance , various enzymatic activity
• Total sodium in body is distributed in two pools
i. Exchangeabale pools- in ECF and ICF
ii. Non-exchangeable pool 40% of na+ is bound to polyanionic proteoglycans
in bone,cartilage,skin etc

6. SODIUM ABSORPTION
• It occurs via two mechanism
1. Freely permeable across the interstitial cell
2. Symport with glucose and amino acids
• It is main determinant of Na+ balance
1. KIDNEYS most efficient and well regulated, elimination if intake and vice
versa ….doesn’t eliminate if there is no sodium intake
2. GASTROINTESTINAL <10% of sodium is lost in feces
3. Sweat glands-insensible loss
SODIUM EXCRETION

7. SODIUM HANDLING OF KIDNEY
• Sodium is reabsorbed at 3 main regions in nephron
A. PCT about 2/3rd of sodium is reabsorbed Sodium
passes along an electrochemical gradient (passive
transport) from the lumen into the tubular cell,
together with water and chloride which also diffuse
passively.
B. TALH around 25-30% is reabsorbed via apical Na-K-
2Cl symporter and Na-H antiporter.
C. DCT In the distal convoluted tubule sodium is
transported against an electrochemical gradient by
sodium-chloride symporters.
D. Some sodium reabsorption occurs in cortical and medullary
collecting ducts

8. REGULATION OF WATER AND SODIUM
EXCRETION
• Circulating level of aldosterone-
• Circulating ANP and other Natriuretic hormones
• Intrarenal level of angiotensin II,PGE
• Tubular secretion of K+ and H+
• ADH and its activity

9. ALDOSTERONE
• IT upregulates and activates basolateral Na+/k+ pumps
• Also upregulates epithelial sodium channels ( ENaCs) in
collecting duct and colon
• Upregulates expression of Na+ CL- cotransporter in DCT
• Factors stimulating release of aldosterone
i. Angiotensin II
ii. Decrease sodium level in ECF
iii. Increase potassium level in ECF
This Photo by Unknown Author is licensed under CC BY
RAAS

10. ATRIAL NATRIURETIC PEPTIDE
• Released from atrium in response to increased atrial stretch via
mechanoreceptors
• Effects
i. Dilates renal blood vessels- increases GFR
ii. Inhibits reabsorption of Na+ from CD
iii. Inhibits release of renin , aldosterone and ADH
iv. Endogenous antagonist of angiotensin II
• Increases excretion of both water and sodium

11. INTRARENAL HORMONES
• Angiotensin II
It stimulates Na+ reabsorption in PCT
Release of Aldosterone from ZG of adrenal cortex
Vasoconstriction of arterioles
• Prostaglandins causes natriuresis by inhibition of ENaCs

12. Antidiuretic hormone(ADH)/Vasopressin/arginine
vasopressin(AVP)
• Produced in Hypothalamus and released via posterior pituitary
• Effect on kidney
1. Increase water permeability of CT, cortical collecting
duct(CCT), outer and inner medullary collecting duct
(OMCD & IMCD) via insertion of aquaporin-2 channels
2. Increase permeability of inner medullary CT to urea and
thus water with it
3. Increase Na+ absorption across loop of henle, adding to
increase water absorption in DCT and CT
• Factors causing secretion
i. Increase serum osmolality(most important)
ii. Angiotensin II

13. REGULATION OF ECF Na+ AND WATER

14. HYPONATREMIA
• It is defined as serum sodium concentration of less than 135 mEq/L
• Joint European guideline classify Hyponatremia in adults as
 Mild 130-134 mEq/L
 Moderate 125-129 mEq/L
 Profound <125 mEq/L
• Hyponatremia have been also classified according to volume status
i. Hypovolemic hyponatremia…….decrease in total body water with greater
decrease in total body sodium
ii. Euvolemic hyponatremia….normal body sodium with increase in total body
water
iii. Hypervolemic hyponatremia….increase in total body sodium with greater
increase in total body water

15. HYPONATREMIA CAUSES
1. Pseudo hyponatremia-
a) Normal plasma osmolality(Isotonic hyponatremia)- normal plasma water is
around 92-94% this water fraction falls in increase of fats and proteins, thus
measured sodium is low
• Hyperlipidemia
• Hyperproteinemia
• Post transurethral resection of prostrate/bladder
b) Increased plasma osmolality(hypertonic hyponatremia)- it is due to
presence of osmotically active molecules in serum resulting in water shift
from ICF to ECF causing dilution of Na+
• Hyperglycemia each 100mg/dl causes 1.6-2.4 mEq/L decrease in Na+
• Mannitol

16. TRUE HYPONATREMIA (hypotonic hyponatremia)
• Based on volume status hyponatremia is classified as
1. HYPOVOLEMIC HYPONATREMIA- there is decrease in TBW with greater
decrease in total body Na+
Primary Na+ loss
RENAL LOSS U(Na+) >20
i. Mineralocorticoid deficiency
ii. Diuretic excess
iii. Osmotic diuresis
iv. Cerebral salt wasting synfrome
EXTRARENAL LOSS U(Na+) <20
i. Burns
ii. Pancreatitis
iii. Diarrhoea and vomitting

17. 2. EUVOLEMIC HYPONATREMIA-normal to low Na+ with increase in
TBW, it is associated with nonosmotic and non-volume related ADH
secretion seen in
i. Glucocorticoid deficiency
ii. Drugs
iii. SIADH
iv. Stress ,surgery
v. Hypothyroidism
vi. Beer potomania

18. 3. HYPERVOLEMIC HYPONATREMIA- increase in Na+ with greater
increase in TBW decrease Na+ concentration
the causative disorder can be differentiated by urinary Na+
Na+ Avid state U(Na+) < 20
i. Liver cirrhosis
ii. Nephrotic Syndrome
iii. Cardiac failure
Renal cause U(Na+) >20
i. Acute or Chronic renal failure

19. Effect of hyponatremia on brain and adaptive response

20. CLINICAL FEATURES
• HISTORY
Exercise associated hyponatremia(in Hot climate and ingestion of fluids)
Medical history of OTC drugs(antipsycotic,antiepileptic,antidepressants)
Dieatry history (salt,protein,water and parentral fluid in hospital case)
• Symptoms varies from Nausea/malaise (mild) to lethargy,seizure (very
low <115 mEq/L
• Gradual fall in Na+ is well tolerated
• Clinical manifestations of hyponatremia results from osmotic water
shifting to ICF……causing
i. Cerebral edematentorial herniationbrainstem compression Death
ii. Non cardiogenic pulmonary edema normocapneic respiratory failure

21. Clinical features cont…..
• Bad prognosis- underlying neurological or metabolic disorder
• Few common symptoms are
i. Stupor/altered sensorium
ii. Anorexia/nausea/vomitting
iii. Lethargy
iv. Decrease tendon reflex
v. Limb weakness
vi. Orthostatic hypotension
vii. Seizure/headache
viii. Stomach cramps

22. • Premenopausal women are prone to developing cerebral edema in
association with hyponatremia due to inhibition of Na-k ATPase by
estrogen and progesterone, may also be caused by hypothalamic and
pituitary infarction
• Hyponatremia in cortisol deficiency occurs due to hypersecretion of
ADH
• Beer potomania The low solute content of beer, and suppressive
effect of alcohol on proteolysis result in reduced solute delivery to the
kidney. The presence of inadequate solute in the kidney eventually
causes dilutional hyponatremia secondary to reduced clearance of
excess fluid from the body
•

23. CEREBRAL SALT WASTING
• It is a rare salt wasting disorder secondary to intracranial pathology as
SAH, Meningitis, carcinoma, post neurosurgery/intervention
• Damage to sympathetic neural input to kidney
• Signs and symptoms are
i. polyuria, defined as over three liters of urine output over 24 hours in an
adult)
ii. high amounts of sodium in the urine
iii. low blood sodium concentration
iv. excessive thirst (polydipsia)
v. extreme salt cravings
vi. dysfunction of the autonomic nervous system (dysautonomia), and
dehydration

24. • CSWS is a diagnosis of exclusion and is difficult to distinguish from the
SIADH, The main clinical difference is that of total fluid status of the
patient: CSWS leads to a relative or overt low blood volume, whereas
SIADH is normal or high blood volume (due to water reabsorption via
the V2 receptor).Urine output is classically low in SIADH and elevated
in CSWS
• CSWS occurs within the 1st week after brain injury and spontaneously
resolves in 2–4 weeks, can last for months or years.
• CSWS is treated by replacing the urinary losses of water and Na+ with
hydration and sodium replacement.
• The mineralocorticoid medication fludrocortisone can also improve
the low sodium level

25. SIADH- Syndrome of inappropriate ADH secretion
• Marked by continued secretion or activity of ADH, despite normal or
increased plasma volume
• Water retention ,hyponatremia , hypoosmolality and high urine
osmolality is hallmark feature
• Signs and symptoms
 Depend on rate and severity of hyponatremia
 Signs of AVP secretion…chronic pain ,pulmonary or CNS symptoms or drug
use
• Investigations
 Serum Na+, K+,Cl-, HCO3, Cr, BUN, Uric acid, blood glucose
 Serum osmolality
 Urine osmolality

26. Diagnosis of SIADH – barter-schwartz criteria 1967
• Hyponatremia with hypoosmolality
• Continued renal Na+ excretion
• Urine less than maximum diluted
• Absence of signs of volume depletion
• Absence of other cause of hyponatremia-mineralocorticoid deficiency
hypothyroidism ,CHF ,CLD ,ESRD , drugs
• Correction of hyponatremia with fluid restriction

27. WORKUP
• Three essential test to differentiate cause of hyponatremia
i. Urine osmolality-Impaired water clearance(>100mOsm/kg) Vs primary
polydipsia
ii. Serum osmolality- True vs pseudohyponatremia
iii. Urinary sodium concentration- hyponatremia secondary to hypovolemia
{U(Na+)<25 mEq/L} vs SIADH {U(Na+) >20-40 mEq/L}
• Ancilary test
i. Serum uric acid SIADH and CSW (autocorrection with Na+ correction in
SIADH)
ii. TSH and Serum Cortisol
iii. Serum albumin, Triglycerides, Blood glucose, Serum K+
iv. ECG

28. • Imaging
i. Head CT in suspected CSW
ii. Chest CT or Xray in selected case of SIADH

29. DIAGNOSTIC APPROACH TO HYPONATREMIA

30. Management
Hypovolemic hyponatyremia most common
• Acute hyponatremia <48hrs- can be corrected rapidly than chronic
hyponatremia > 48hrs duration
• In pseudohyponatremia (isotonic and hypertonic ) treat underlying
diseases
• Infuse saline to correct hypovolemia  decrease activity of AVP
• Replace K+ if due to diuretic use

31. Hypervolemic Hyponatremia
• Salt and fluid restriction
• Loop diuretics with salt tablets
• Correct underlying condition
• V2 antagonist may be considered
Euvolemic Hyponatremia
• Asymptomatic- fluid restriction <1 litre/day
Severe symptomatic hyponatremia 3% NaCl can be used

32. OSMOTIC DEMYELINATION SYNDROME
• During chronic hyponatremia—efflux of organic osmolytes(Cr,Betaine,
taurine)
• While rapidly correcting hyponatremia (>10mmol/L/day) there is re
accumulation of organic osmolytes causing degenerative loss of
oligodendrocyte
• Rapid correction of hyponatremia causes disruption of BBB adding to
demyelinosis
• Risk factor for developing ODS
i. Alcoholism,malnutrition
ii. Neurological symptoms (seizure,stupor,coma)
iii. Metabolic underlying cause
iv. Chronic hyponatremia

33. Type of lesion in ODS
1. Pontine-
i. occurs 2-3 days after overcorrection of hyponatremia
ii. Presents as paraparesis, Quadriparesis ,dysphagia ,dysarthia, diplopia and
locked in syndrome
2. Extrapontine
i. Lesion could be cerebellum, LGB, thalamus, Putamen, Cerebral cortex
ii. Signs and symptoms are ataxia, mutism, parkinsonism, dystonia and
catatonia

34. Guideline
Joint European clinical practice guideline on diagnosis and treatment of hyponatremia
• Three parameters determine treatment guidelines
i. Patient’s volume status
ii. Duration and severity of hyponatremia
iii. Severity of clinical symptoms
• Acute/chronic severely symptomatic hyponatremia
i. Promptly infuse 150ml 3% NaCl IV over 20 min repeat max 3 times, check
Na+ before repeating
ii. If patient improves with 5mmol/L increase in 1st hour
a. Limit increase in Na+ by 10mmol/L in 24hr and 8mmol/L in next any 24 hrs
b. Check Na+ 6 hourly
iii. If no improvement
a. Control increase infusion @ 1mmol/L /hr
b. Stop if Na+ 130mEq/l or condition improves or total increase is 10mmol/L
c. Check Na+ 4 hourly till hypertonic saline is being used

35. • Acute hyponatremia with mild or moderate symptoms
i. Rule out error of measurement
ii. water restriction and stop hyponatremia causing drugs
iii. Workup for cause
iv. If acute decrease of Na exceeds 10mmol/L may infuse a single infusion of 150ml 3%NaCl
over 20min
v. Recheck Na+ after 4hrs
• In chronic hyponatremia with mild or moderate symptoms
i. Stop non-essentials fluids medications provoking hyponatremia
ii. In moderate to profound hyponatremia avoid increase of serum Na >10mmol/L in 1st 24hrs
and >8mmol/L in next every 24hrs to prevent ODS

36. • Hypervolemic hyponatremia
i. Treatment of underlying cause ,correction of hypokalemia
ii. Fluid restriction to prevent further fluid overload
iii. AVP antagonist as vaptans are highly effective in HF, liver disease
beside SIADH (max duration 1-2 mnths)
iv. Therapy with vaptans should be initiated in hospital setting with
liberalisation of fluid intake >2litre/day with close monitoring of
plasma Na+
Tolvaptan V2antagonist- oral
Conviptan iv use V1a/V2 antagonist

37. For patient with SIADH
i. In moderate to profound hyponatremia consider fluid restriction as
first line treatment
ii. In moderate or profound hyponatremia, solute intake @ 0.25-0.50
g/kg per day with low dose loop diuretics (furosemide 20mg twice
daily) as second line of treatment
iii. In moderate and profound hyponatremia demeclocycline, Vaptans,
lithium is not advised
iv. Demeclocycline a potent inhibitor of principal cell,used in cases
where Na doesn’t increase with furosemide and salt tablets,
nephrotoxic(decrease GFR) and also avoided in liver disease

38. Hypovolemic hyponatremia
i. Restore ECF with 0.9% NaCl or a balanced crystalloid at 0.5-
0.1ml/kg/hr
ii. If hemodynamicly unstable rapid fluid resuscitation
iii. The traditional approach is to calculate Na+ deficit
Na+ deficit = 0.6 * BW* (target Na+ -plasma Na ) and replenish at fixed rate
iv. Na+ should be monitored every2-3 hrs during treatment
v. IV loop diuretics helps in relieve from symptoms due to acute
pulmonary edema

39. • If hyponatremia is corrected too rapidly consider
i. Promptly lower Na if increase is >10mmol/L in 1st 24hrs or >8mmol/L in any
24hrs thereafter
ii. Discontinue the active treatment
iii. Consider infusion of 10ml/kg of electrolyte free water over 1hr with strict
monitoring of urine output and fluid balance
iv. Consult to consider to add desmopressin 2mcg,not to be repeated before
8hrs

40. HYPERNATREMIA

41. HYPERNATREMIA
• It is defined as plasma Na+ concentration > 145 mEq/L
• Less common than hyponatremia but with mortality 40-60%

42. CAUSES
• Inadequate water Intake
i. Impaired thirst
ii. Decrease access to fluid (elderly with mental illness)
iii. Increase insensible loss
• Increase water loss
i. GI Loss- vomiting, diarrhoea(secretory and viral gastroenteritis)
ii. Renal loss- Central diabetes insipidus, osmotic diuresis(hypercalcemia, hyperglycemia )
Nephrogenic DI
• Excessive sodium
i. Iatrogenic- hypertonic saline, NaHCO3 tablets
ii. Mineralocorticoid excess- cushing, primary aldosteronism, ectopic ACTH
iii. Peritoneal dialysis- loss of water> loss of sodium
• Drugs/medication- alcohol, lithium, phenytoin, sulfonylurea, colchicine

43. Effects of hypernatremia on brain and adaptive response

44. Clinical signs of hyponatremic states related to
serum osmolality
• Osmolality (mOsm/kg) Manifestations
i. 350-375
ii. 375-400
iii. 400-430
iv. > 430
Restlessness, irritability
Ataxia, tremulousness
Hyperreflexia, twitching, spasticity
Seizures and Death

45. • Most hyponatremia in emergency is related to severe volume loss
• In healthy patients, hypovolemia causes conservation of free water by
kidney
i. low Urine output (<20ml/hr) with
ii. high osmolality (>1000 mOsm/kg water)
• Diabetes Insipidus
i. Failure of central or peripheral ADH response NDI
ii. Urine osmolality is low(200-300 mOsm/kg)
iii. Urinary [Na+] 60-100mEq/kg
iv. Large urine volume >50ml/kg/day

46. WORKUP
• History- diarrhoea, thirst, polyuria
• Documentation of Input Output in hospitalised cases
• Laborotary investigation
 Serum and urine osmolality
 Urine Electrolytes
• DI requires measurement of urine osmolality to DDAVP
• AVP assay to differentiate between Central DI and NDI
 In pregnancy drawn in Vial containing 1,10- phenthroline
Inhibits placental vasopressinase

47. Diagnostic approach to hypernatremia
• Figure source harrison’s

48. Treatment
• Withdraw causative agent- hyperglycemia, hypercalcemia ,hypokalemia, diarrhoea
• Correct slowly to avoid cerebral edema by correcting “free water
deficit over 48 hrs or max @ 10 mmol/day
• In acute hypernatremia(<48hrs) can correct rapidly @ 1mmol/hr
• Oral route is preferred for volume correction
• IV fluid
i. Treat initially with 0.45% saline
ii. Then with D5W (preferred)

49. Treatment
• Additional drugs – mostly used in chronic management of polyuria
DDAVP(artificial AVP) desmopressin – oral, intranasal, Iv
Amiloride (2.5-10 mg/d) in Lithium induced NDI
NSAIDS inhits intrarenal PGE
Thiazides reduces polyuria in NDI

50. Management of Hypernatremia
• Source Harrison

51. GUIDELINES
• Society of endocrinology guideline for diabetes insipidus
i. In CDI with unconsciousness check volume status every 12 hourly and daily
maintenance of Input-Output chart, daily Na+
ii. Measure Na+ every 4 hourly during fluid resuscitation and later at least 12
hourly
iii. In patient with High Urine Output and low urine osmolality consider
desmopressin (DDAVP)
iv. First goal is fluid optimization then asses for DDAVP therapy
v. Correction rate in acute symptomatic hypernatremia @ 5mmol/L in 1st hour
if asymptomatic rate @ 0.5 mmol/hr
vi. Maximum rate of correction in 24hrs is 10mmol/L

52. TAKE HOME MESSAGE
• History of duration of hypo/hypernatremia is very important in
management
• Rate of correction in hyponatremia should keep in mind risk of ODS
• CSW Vs SIADH (intracranial pathology) can be differentiated with
urine Na+ increased in SIADH
• V2 antagonist-vaptans should be initiated in hospital setting with
liberalisation of fluid intake >2litre/day
• Regular monitoring of serum Na+ is essential for proper management
in both hypo/hypernatremia
• Central DI and NDI can be differentiated with response to DDAVP and
AVP assay(falls in central DI)

53. THANK YOU