Electrolytes in body fluid, Sodium homeostasis , its related disorders

1. Introduction to Serum
Electrolytes , Sodium
homeostasis & related
disorders
Dr. Ifat Ara Begum
Associate Professor
Dept of Biochemistry
Dhaka Medical College

2. What is electrolyte?
An electrolyte is a chemical compound
that dissociates in a solution in to ions
that conduct electricity
They may be cations (positive charged)
or anions (negative charged)
In living system, each body fluid
compartment is electrically neutral
containing same amount of cations &
anions

3. Cations in ECF & ICF
Points ECF (meq/L) ICF (meq/L)
Cation Na+
: 135-145 10-12
K+
: 3.5-5 140-150
Ca++
: 2-2.5 negligible
Mg++
: 3 40

4. Anions in ECF & ICF
Points ECF (meq/L) ICF (meq/L)
Anions Cl-
: 95-105 3-8
HCO3
-
: 22-28 10-12
PO4
---
: 2 140
Protein: 16 40

5. Function of electrolytes
General functions:
 Maintain body fluid osmolarity
 Maintain integrity of body fluid
compartments
 Concern with RMP & AP
 Concern with neuromuscular
irritability/excitability & tissue
functions

6. Contd
Specific functions:
 May act as cofactor of some enzymes
 May be related with buffering activity:
Bicarbonate , phosphate
 Calcium: Blood coagulation, bone
mineralization etc

7. Serum electrolyte profile with their
reference range
Name of electrolyte Serum conc.
(mmol/L)
Na+
135-145
K+
3.5-5
HCO3
-
22-28
Cl-
98-107

8. Sodium

9. Introduction to sodium
The major cation of ECF
Normal range in ECF: 135-145 mmol/L
Normal range in ICF: 10-12 mmol/L
Major partner of Na+
is Cl-
The primary source of dietary sodium is
sodium chloride or salt,
Sodium salts are one of the important
osmotically active solutes in ECF

10. Contd
Plasma sodium concentration is affected by
change of water balance & is a poor guide of
body Na content
Body Na+
content :
a) ECF volume is the direct function of
body Na content
b) Body Na+
content changes with the
change of Na+
balance (positive /
negative Na balance)

11. Contd
Urinary Na+
excretion depends on ECF
volume , not ECF Na+
concentration
Regulation of Na+
balance is equivalent
to the body fluid volume regulation

12. Function of sodium
Provides 92% of ECF osmolarity &
maintains internal environment
Is concerned with
 RMP, AP & neuromuscular/ tissue
excitability
 Maintenance of electrolyte & fluid
balance
 Cardiac rhythmicity & contractility
 Exocrine secretion
 Maintenance of blood volume & BP

13. Renal handling of sodium
May be discussed under following
headlines:
I. Tubular load of sodium
II. Tubular reabsorption of sodium
III. Renal excretion of sodium

14. i) Tubular load of sodium
Tubular load equals to GFR X Plasma
concentration
= 180 L/day X 140 mmol/L
= 25250 mmol/day

15. ii) Tubular reabsorption of sodium
More than 90% of tubular load
i. From PCT: 60 - 70%
ii. From ALH (thick): 20 – 30%
iii. From DCT: 5% (stimulated by
aldosterone)
iv. From CD: 1- 8% (stimulated by
aldosterone & inhibited by ANP)

16. iii) Renal excretion of sodium
It is 100 200 ml/day
Factors regulating renal sodium
excretion:
 1. GFR :Aldosterone escape
mechanism
 2. ECV : Proportionately related with
renal Na excretion
 3. SNS activity: Stimulation of SNS
reduces renal Na excretion

17. Contd
 4. Hormones :
 Hormones increasing tubular
reabsorption of NaCl , thereby
reducing the renal sodium excretion :
Aldosterone (DCT & CD) ,
Angiotensin II (PCT) , Catecholamine
(PCT)
 Hormones decreasing reabsorption of
NaCl from CD , thereby increasing the
renal sodium excretion: ANP

18. Contd
 5. Peritubular capillary
hemodynamic :
 Increased HP decreases NaCl
reabsorption & increases renal Na
excretion
 Increased COP increases NaCl
reabsorption & decreases renal Na
excretion

19. Contd
 6. Renal vasodilators (like PG, EDRF,
Bradykinin, Dopamine etc) : Increase
GFR & increase Na excretion

20. Sodium homeostasis
(ECF volume homeostasis)
May be discussed under following
headings:
 Body sodium content
 Compartmental distribution of sodium
 Sodium balance
AND
 Regulation of sodium balance (volume
regulation)

21. Body sodium content
3500 – 4500 mmol in adult
or
50 – 60 mmol/kg
[1 mmol of sodium= 23 mg]

22. Compartmental distribution of sodium
I. In ECF : ≥ 90% (usually 95%)
II. In ICF : ≤ 10% (usually 5%)

23. Sodium balance
Intake: 100 – 200 mmol/day via
foods, drinks, added salt
Output: 100 – 200 mmol/day via
a) Urine: 150 mmol/day (major route of
Na excretion
b) Feces: 5 – 10 mmol/day
c) Sweat: 25 mmol/day

24. Regulation of sodium balance
(Volume regulation)
As most of the body Na lies in ECF, so
ECF volume directly depends on total
body Na content.
Body senses the body Na status
indirectly by sensing the ECF volume
status through baroreceptors
Recognition of Na status signals the
kidney to respond accordingly
a) To retain salt & water (in Na deficit)
b) To excrete salt & water (in Na excess)

25. Contd
i.e. for Na regulation, there are
a) Afferent limb (sensor/sensing
mechanism)
b) Efferent limb (effector organ)

26. Contd
Afferent limb/sensor/sensing
mechanism:
 Baroreceptors present in atria ,
carotid sinus, aortic arch , great veins
& afferent arteriole of kidney act as
afferent limb
 They are :
 Stimulated by: volume expansion
(increased body Na content)
 Inhibited by volume contraction

27. Contd
Efferent limb/effector organ:
 Kidney acts as efferent limb/effector
organ
 They respond to volume status (body
Na content) by NaCl retention
/excretion and its regulation

28. Events following excess NaCl intake
Excess NaCl intake
Hypervolemia
Stimulation of baroreceptors
Inhibition
of SNS
Inhibition
of RAAS
Increased
secretion
of ANP

29. Contd
Inhibition
of SNS
Inhibition
of RAAS

↓Catecholamine
release
 ↓NaCl
reabsorp.
 Renal
vasodilatation
 ↑GFR leading
to aldosterone
escape
 ↓production
of renin,
angiotensin II,
aldosterone

30. Contd
All these events finally causes salt &
water excretion to normalize the ECF
volume by:
i. Decreased catecholamine, angiotensin
II & aldosterone
ii. Increased ANP
iii. Increased GFR & aldosterone escape

31. Events following decreased NaCl
intake
Reduced NaCl intake
Hypovolemia
Inhibition of baroreceptors
Stimulatio
n of SNS
Stimulation
of RAAS
Decreased
secretion
of ANP

32. Contd
Stimulatio
n of SNS
Inhibition
of RAAS
 Catecholamine
release
 ↑NaCl
reabsorp.
 Renal
vasoconstriction
 ↓GFR leading
to failure of
aldosterone
escape
 ↑production
of renin,
angiotensin II,
aldosterone

33. Contd
All these events finally causes salt &
water retention to normalize the ECF
volume by:
i. Increased catecholamine, angiotensin
II & aldosterone
ii. Decreased ANP
iii. Decreased GFR & failure of
aldosterone escape

34. Osmoregulation versus Volume
regulation
Features Osmoregulation Volume
regulation
Sensor Osmoreceptor Baroreceptor
Sensed stimulus ECF osmolarity ECF volume
Effector organ Kidney Kidney
Effector/mediator ADH & thirst Aldosterone, ANP,
Angiotensin II,
Catecholamine,
GFR

35. Contd
Features Osmoregulation Volume
regulation
Effect (end point
of regulation)
Regulation of
renal water
excretion and
water intake
Regulation of renal
Na excretion
Pattern of
response
Quick Slow

36. Aldosterone escape
It is the phenomenon characterized by
excessive urinary Na+
excretion despite
maximum aldosterone activity in CD
It happens following hypervolemia of
any cause, due to
 Increased tubular load of Na+
 Increased ANP secretion

37. Contd
Following
hypervolemia,
there is ↑ ANP
Following
hypervolemia, there is
↑ GFR & ↑ tubular load
of Na+
Decreased Na+
reabsorption in CD
↑ Na+
delivery to distal
nephron despite utmost Na+
reabsorption from PCT
 In CD, Na+
load becomes
more than maximum
capacity of aldosterone to
reabsorb Na+
Na+
appears in urine by escaping aldosterone

38. Abnormalities of sodium homeostasis
2 types of abnormalities:
1. Hypernatremia
2. Hyponatremia

39. 1. Hypernatremia
The clinical state of elevated Na+
concentration (>145 mmol/L)
Occurs mostly due to water imbalance ,
not Na+
imbalance
Always associates with
hyperosmolarity
Its causes lead to development of
hyperosmolar state in ECF

40. Contd
Acute hypernatremia develops
following
 Rapid infusion of hypertonic saline or
sodium bicarbonate
 Sea water intake

41. Contd
Pathophysiological types of
hypernatremia:
a. Clinically euvolemic
b. Hypervolemic
c. Hypovolemic

42. Point Euvolemic Hypervolemic Hypovolemic
Osmolarity
of plasma
High (>295
mosm/L)
High (>295
mosm/L)
High (>295
mosm/L)
Body total
Na+
content
Normal High Low
Common
causes
DI, reduced
water intake
Excess infusion
of hypertonic
saline, Sea
water intake,
Conn’s
/Cushing
syndrome etc
S. diarrhoea/
burn,
persistent
vomiting,
profuse
sweating , salt
losing

43. Lab evaluation of hypernatremia
Euvolemia Hypernatremia Hypervolemi
a
Hypovolemia
Oligouria
(non-renal cause)
Polyuria
(renal cause)
DI
Conditions
leading to
Hypertonic
hypervolemia

44. Clinical consequences or S/S of
hypernatremia
It may be

Acute :Develops in ≤ 48 hours & more
serious

Chronic : Develops over 48 hours . Less and
well tolerated
S/S appears when serum concentration of
sodium is >155 mmol/L
S/S is due to cellular dehydration (esp.
cerebral dehydration)

45. Contd
If person is awake & alert: Thirst is the
prominent symptom
Other S/S include anorexia, nausea, vomiting,
altered mental status, neuromuscular
hyperactivity, agitation, irritability, lethargy,
stupor, convulsion, coma, even death

46. 2. Hyponatremia
The clinical state of decreased Na+
concentration (<135 mmol/L)
The commonest electrolyte disorder in
clinical practice
Occurs mostly due to water imbalance ,
not Na+
imbalance
Usually (not always) associates with
hypoosmolarity

47. Contd
Pathophysiological types of
hyponatremia:
a. Isotonic hyponatremia
b. Hypertonic hyponatremia
c. Hypotonic hyponatremia: 3 types
Hypervolemic Hypovolemic Euvolemic

48. Point Isotonic
hyponat.
Hypertonic
hyponat.
(dilutional/
translocational
hyponat.)
Osmolarity of
plasma
Normal (280-
295 mosm/L)
High (>295
mosm/L)
Body total Na+
content
Normal (clinically
euvolemic)
Normal (clinically
euvolemic)
Common causes Pseudo-
hyponatremia
ARF, uncontrolled
DM, acute alcohol
poisoning, infusion
of mannitol/ sorbitol/
AA etc

49. Point Euvolemic
hypotonic
hyponat.
Hypervolemic
hypotonic
hyponat.
Hypovolemic
hypotonic
hyponat.
Osmolarity of
plasma
Low (<280
mosm/L)
Low (<280
mosm/L)
Low (<280
mosm/L)
)
Body total
Na+
content
Normal High Low
ECF volume Normal Increased
(oedema +)
Decreased
(dehyd.+)

50. Point Euvolemic
hypotonic
hyponat.
Hypervolemic
hypotonic
hyponat.
Hypovolemic
hypotonic
hyponat.
Common
causes
SIADH,
psychogenic
polydypsia,
hypothyroidism,
Addison’s
disease etc
Edematous
states , i.e.
CCF, NS,
Advanced RF,
Hepatic failure,
Kwashiorkor ,
cirrhosis of liver
etc
Renal/extra-
renal salt &
water loss
treated by
hypotonic fluid
or any i/v fluid
without Na

51. Lab evaluation of hyponatremia

52. Clinical consequences or S/S of
hyponatremia
Severity depends on
 Severity of hyponatremia
 The rate at which sodium concentration is
reduced
It may be

Acute :Develops in ≤ 48 hours & more severe
degrees of cerebral oedema may occur
 Chronic : Develops over 48 hours . Less and
well tolerated cerebral oedema

53. Contd
S/S appears when

Serum concentration of sodium is <120
mmol/L
 Or when sodium level is decreased rapidly
S/S is due to cellular overhydration (esp.
cerebral edema)

54. Contd
S/S includes:
• CNS: Lethargy, headache, disorientation,
drowsiness, confusion, convulsion, coma,
even death
• GIT: Anorexia, nausea, vomiting etc
• Musculoskeletal : Cramps, sluggish deep
tendon reflex etc

55. Related
topics

56. Pseudo hyponatremia
The artificial lowering of plasma sodium
concentration because of increased solid
phase (formed by plasma protein & lipids) of
plasma
[In normal individual, solid phase is ignored
& 1 L plasma is assumed to be equivalent to
1 L water where 140 mmol/L Na+
is found]

58. Contd
Here Na+
concentration per liter of plasma
water is normal , so patient shows the status
of isotonicity
Common causes:
Hyperlipidaemia (hypertriglyceridemia,
hypercholesterolemia )
Hyperproteinemia (e.g. multiple
myeloma or i/v infusion of immunoglobulin)
etc

59. Dilutional/translocational
hyponatremia
Different osmotically active substances
accumulate in plasma (like glucose in DM,
urea in ARF etc)
Increased ECF OP in comparison to that of ICF
Water from ICF comes to ECF
Hyponatremia

60. SIADH
A condition characterized by excessive
release of ADH from pituitary gland or
another source, causing the body to
retain fluid and lower the blood sodium
level by dilution.
It is mainly caused by cancer, esp. that
of the lungs

61. Acute dilutional hyponatremia
Hyponatremia develops within 48 hours due
to addition of water to ECF
Causes:
Excessive i/v fluid infusion
Fresh water drowning
Psychogenic polydypsia
Post operative period (due to ↑ADH release)
Acute hyperglycemia
ARF

62. Hyperosmolar state
Clinical condition leading to ECF
hyperosmolarity
Causes:
 All causes of hypertonic hyponatremia
 All causes of hypernatremia

63. Hypoosmolar state
Clinical condition leading to ECF
hypoosmolarity
Causes:
 All causes of hypotonic hyponatremia
(consider volume status)
 Excessive hypotonic fluid infusion
 Fresh water drowning
 Psychogenic polydypsia
 Postoperative period

64. Diabetes Insipidus
Clinical condition characterized by polyuria
due to ADH deficiency/resistance
It may be :
a. Central DI: If the cause is ↓ADH release
from hypothalamus
b. Nephrogenic DI: If the cause is resistance of
CD to ADH

65. Contd
Causes of central DI Causes of nephrogenic DI
 Genetic
 CNS disorders : Tumour,
TB, encephalitis, head injury
etc
 Idiopathic
 Genetic
 Heavy metal poisoning
 Renal disease like
Interstitial nephritis etc
 Hypokalemia
 Hypercalcemia

66. Contd
Common lab findings:

Urine volume: >10 L/day (Polyuria)

Urinary osmolarity: <150 mosm/L
[After ADH analogue injection: if Uosm is
>750 mosm/L , it is central DI
If no improvement, its nephrogenic DI]

67. Contd
 Mild hypernatremia: if volume depletion is
present
 Basal serum ADH conc.
In central DI: Low
In nephrogenic DI: High
 Plasma osmolarity: Maintained at near
normal by water intake due to increased
thirst

Urinary sodium: >20 mmol/L