REGULATION OF VOLUME AND TONICITY OF ECF

Dr.AnuPriya J

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

• 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.

Introduction

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

Body composition

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

Basic principles

• Plasma osmolality = 2(Na+) + 2(K+) + urea + glucose• Simplified asPlasma 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.

Regulation of OsmolalityWater 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

Regulation of OsmolalityIncreased Osmolality of ECF

Increased thirst

Dilution 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

Increased Osmolality of ECF

Dr.Anu Priya

set point change for osmolality - berne n Levy pg 597 Ch 34

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

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.

Regulation of volume

Regulation of volumeEFFECTIVE 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

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

Regulation of volume

Regulation of volume

SODIUM BALANCE

Input • Food & water 100-400 mmol/day

Output • Urine100-400mmol/day• Sweat & feces -

negligible

• 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.

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

Four parallel effector pathways

•Renin – angiotensin aldosterone

•Sympathetic division of ANS

•Post.pituitary - ↑ se AVP(ADH – Antidiuretic hormone)

•Atrial Natriuretic Peptide

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

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.

Effects of Angiotensin II

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

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).

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).

• Inhibition of NaCl reabsorption by the collecting duct.

• Inhibition of ADH secretion and its action on the collecting duct.

Natriuretic peptides

Salt appetite

• Some areas in the same region where thirst and ADH osmoreceptors are located.

• 2 primary stimuli that increase salt appetitea. Decreased ECF sodium concentrationb. Decreased blood volume or blood pressure

associated with circulatory insufficiency

Change in osmolality affects cell function

• Hyperosmolality

• Hypoosmolality

Central pontine myelinolysis

Edema

• Increased ECF volume

• Decreased effective circulating volume

• Examples

Iso-osmotic volume expansionCauses• Infusion of isotonic fluids

Causes• Diarrhoea • Vomiting • Haemorrhage • Burns

Iso-osmotic volume contraction

Applied

Hyper-osmotic volume expansion

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

Applied

Hypo-osmotic volume expansion

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

Applied

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