REGULATION OF VOLUME AND TONICITY (OSMOLALITY) OF EXTRACELLULAR FLUID - PHYSIOLOGY AND APPLIED.

1. REGULATION OF VOLUME AND
TONICITY OF ECF
Dr.AnuPriya J

2. Scheme
• Introduction
• Extracellular fluid (ECF)
• Regulation of Osmolality of ECF
-Water balance
-Role of ADH & thirst mechanism
-Role of osmoreceptors & volume receptors
• Regulation of volume of ECF
-Sodium balance
-Effective circulating volume & volume sensors
-Regulation of sodium balance
• Applied aspects

3. Introduction
• It is important to regulate ECF volume to maintain
blood pressure, essential for adequate tissue
perfusion & function.
• Changes in extracellular osmolality cause changes in
cell volume that seriously compromise cell function
especially in the CNS.

4. Introduction
• Regulation of body fluid volume and osmolality
(water and electrolyte balance) is an integrated
function of various organ systems
• Kidneys play a major role

6. Body composition

7. Constituents and their contribution
to plasma osmolality
Constituent (Solute - ion) Osmolality (mOsm/kg H2O)
Sodium 135-145
Potassium 3.5-5
Chloride 95-110
Calcium 2.2-2.6
Phosphate 4
Proteins 5
Sulphate 1
Bicarbonate 22-26
PLASMA OSMOLALITY 280-295

8. Basic principles
• Plasma osmolality
= 2(Na+) + 2(K+) + urea + glucose
• Simplified as
Plasma osmolality (mmol/kg)= 2 x plasma Na+ (mmol/L)
• Sodium and its associated anions make the largest contribution
to plasma osmolality.
• Water balance in the body is the most important determinant
of the body fluid osmolality.

9. Regulation of Osmolality
Water balance
INPUT
 Food 800-1000ml/day
 Oxidation of food
300-400ml/day
 Liquid 1-2L/day (highly
variable)
TOTAL 2100-3400ml/day
OUTPUT
 Insensible loss
800-1000ml/day
 Sweat
200ml (highly variable)
 Feces 100-200ml/day
 Urine
1-2L/day(highly variable)
TOTAL 2100-3400ml/day

10. Regulation of Osmolality
Increased
Osmolality of ECF
Stimulation of thirst
osmoreceptors
Increased thirst
Increased water
intake
Increased Osmolality of ECF
Dilution of ECF
Decreased Volume of
ECF
Stimulation of ADH
osmoreceptors
Increased ADH secretion
Water retention due to increased
water permeability in distal tubules
and collecting ducts
Dilution of ECF

16. Regulation of volume
• Na+ content in the body is the main
determinant of ECF volume.

17. Regulation of volume
• Oral sodium intake = Renal sodium out put + Extra renal
sodium out put .
• Kidneys excrete or conserve sodium in response to increase or
decrease in ECF volume not changes in ECF sodium
concentration.
• It is not ECF volume per se , but effective circulating
volume that regulates sodium excretion.

20. Regulation of volume
EFFECTIVE CIRCULATING VOLUME (ECV)
• The portion of the ECF volume that is contained within the
vascular system and is effectively perfusing the tissues.
• Regulation of ECV is closely related with regulation of sodium
balance.
• ECV reflects the activity of volume sensors located in the
vascular system.
• Kidneys play a major role

21. Regulation of volume
SODIUM BALANCE
• Sodium is actively pumped out of the cells by Na+-K+ ATPase
pump.
• 65% of total body Na+ is extracellular.
• ECF volume is the reflection of total body Na+ content.
• Normal volume regulatory mechanisms ensure that Na+ loss
balances Na+ gain

22. Regulation of volume
SODIUM BALANCE
Input
• Food & water
100-400 mmol/day
Output
• Urine100-400mmol/day
• Sweat & feces -
negligible

23. • For an expansion in ECF volume to stimulate Na+
excretion,
the expansion must make itself evident in the part of
the ECF compartment where the ECF volume sensors
are located.
• The thoracic blood vessels appear to be the site of
greatest importance.

24. ECF Volume Receptors
 “Central” vascular sensors
• Low pressure sensors
Cardiac atria
Pulmonary vasculature
• High pressure sensors
Carotid sinus
Aortic arch
Juxtaglomerular apparatus(renal afferent arteriole)
 Sensors in the CNS
 Sensors in the Liver

25. Four parallel effector pathways
• Renin – angiotensin aldosterone
• Sympathetic division of ANS
• Post.pituitary - ↑ se AVP(ADH – Antidiuretic hormone)
• Atrial Natriuretic Peptide

30. Effects of Angiotensin II
1. Aldosterone release.
2. Vasoconstriction of renal and other systemic
blood vessels.
3. Stimulation of thirst and ADH secretion.
4. Increased Tubuloglomerular feedback

31. Effects of Angiotensin II
5. Enhancement of NaCl reabsorption by
the proximal tubule, thick ascending limb of
Henle’s loop, the distal tubule and the collecting duct.
• Directly by stimulating apical Na+-H+ exchange in
tubule cells.
• Indirectly by lowering renal plasma flow.

33. Effects of Aldosterone
• Stimulates NaCl reabsorption by the
o thick ascending limb of loop of Henle,
o distal tubule and collecting duct (aldosterone-sensitive distal
nephron)
ENaC

34. Renal sympathetic nerve activity
 Afferent and efferent arteriolar vasoconstriction
(α adrenergic receptors) → →decreased GFR → filtered load
of Na+ to the nephrons is reduced.
 Renin secretion stimulated by the cells of the afferent
arterioles (β adrenergic receptors).
 NaCl reabsorption along the nephrons is directly stimulated
(α adrenergic receptors).

35. Natriuretic peptides
• Vasodilation of afferent arteriole and
Vasoconstriction of efferent arteriole → increases
GFR → increased filtered load of Na+
• Inhibition of renin secretion by the afferent
arterioles.
• Inhibition of aldosterone secretion (directly and
indirectly via inhibition of renin secretion).

36. Natriuretic peptides
• Inhibition of NaCl reabsorption by the collecting
duct.
• Inhibition of ADH secretion and its action on the
collecting duct.

37. Salt appetite
• Some areas in the same region where thirst and ADH
osmoreceptors are located.
• 2 primary stimuli that increase salt appetite
a. Decreased ECF sodium concentration
b. Decreased blood volume or blood pressure
associated with circulatory insufficiency

40. Change in osmolality affects cell function
• Hyperosmolality
• Hypoosmolality

41. Edema
• Increased ECF volume
• Decreased effective circulating volume
• Examples

42. Applied
Iso-osmotic volume expansion
Causes
• Infusion of isotonic fluids
Iso-osmotic volume contraction
Causes
• Diarrhoea
• Vomiting
• Haemorrhage
• Burns

43. Hyper-osmotic volume
expansion
Applied
Hyper-osmotic volume
contraction
Causes
• Excessive amount of
hypertonic saline
Causes
• Decreased water intake
• Diabetes mellitus
• Diabetes insipidus
• Excessive sweating
• Alcoholism
• In tracheostomy patients,
insensible water loss – upto
500ml via lungs

44. Hypo-osmotic volume
expansion
Applied
Hypo-osmotic volume
contraction
Causes
• SIADH
• Ingestion of large volume of
water
• Excessive infusion of
hypotonic saline
• Nephrogenic syndrome of
inappropriate antidiuresis
• Rectocolonic washouts
with plain water
Causes
• Adrenocortical insufficiency
(renal loss of NaCl)
• Vomiting
• Aspiration of gastric
secretions

45. References
 Berne & Levy - Physiology, 6th Edition
 Boron & Boulpaep - Medical Physiology, 2nd Edition
 Best & Taylor's Physiological Basis Of Medical Practice, 13/ E.
 Guyton And Hall Textbook Of Medical Physiology 12th Edition
 Ganong’s Review Of Medical Physiology 24th Edition
 Harrison's Principles Of Internal Medicine 18th Edition
 Textbook of Medical physiology by Prof GK Pal 2nd edition
 Internet References