CONTROL OF EXTRACELLULAR
FLUID OSMOLARITY AND
• Regulation of extracellular fluid osmolarity and sodium
concentration are closely linked because sodium is the most
abundant ion in the extracellular compartment.
• Plasma sodium concentration is normally regulated within close
limits of 140 to 145 mEq/L.
• Sodium ions and associated anions (primarily bicarbonate and
chloride) represent about 94 percent of the extracellular
osmoles, with glucose and urea contributing about 3 to 5
percent of the total osmoles.
• Two primary systems are especially involved in regulating the
concentration of sodium and osmolarity of extracellular fluid:
(1) The osmoreceptor-ADH system.
(2) The thirst mechanism.
ADH synthesis in supraoptic and paraventricular
nuclei of the hypothalamus and ADH release
from the posterior pituitary.
• STIMULATION OF ADH RELEASE BY:
1. Increased osmolarity.
2. Decreased arterial pressure.
3. Decreased blood volume
2- IMPORTANCE OF THIRST IN CONTROLLING
EXTRACELLULAR FLUID OSMOLARITY AND
• The kidneys minimize fluid loss during water
deficits through the osmoreceptor-ADH feedback
• Adequate fluid intake, however, is necessary to
counterbalance whatever fluid loss does occur
through sweating and breathing and through the
• Many of the same factors that stimulate ADH
secretion also increase thirst, which is defined as
the conscious desire for water.
• STIMULI FOR THIRST:
1. Increased extracellular fluid osmolarity, which causes intracellular
dehydration in the thirst centers, thereby stimulating the sensation of
2. Decreases in extracellular fluid volume and arterial pressure also
3. A third important stimulus for thirst is angiotensin II.
4. Dryness of the mouth and mucous membranes of the esophagus can
elicit the sensation of thirst.
5. Gastrointestinal and pharyngeal stimuli influence thirst.
After a person drinks water, 30 to 60 minutes may be required for the water to be
reabsorbed and distributed throughout the body. If the thirst sensation were not temporarily
relieved after drinking water, the person would continue to drink more and more, eventually
leading to overhydration and excess dilution of the body fluids.
• Renal Regulation of Potassium, Calcium,
Phosphate, and Magnesium.
• Integration of Renal Mechanisms for Control of
Blood Volume and Extracellular Fluid Volume.
1- Regulation of extracellular fluid potassium
concentration and potassium excretion:
• Extracellular fluid potassium concentration normally is
regulated at about 4.2 mEq/L.
• Maintenance of balance between intake and output of
potassium depends primarily on excretion by the kidneys.
• The most important factors that stimulate potassium
secretion by the principal cells include:
(1) Increased extracellular fluid potassium
(2) Increased aldosterone.
(3) Increased tubular flow rate.
• One factor that decreases potassium secretion is
increased hydrogen ion concentration (acidosis).
Renal potassium excretion is determined by the sum of
(1) the rate of potassium filtration (glomerular filtration
rate [GFR] multiplied by the plasma potassium
(2) the rate of potassium reabsorption by the tubules, and
(3) the rate of potassium secretion by the tubules.
Increased dietary potassium intake and increased
extracellular fluid potassium concentration stimulate
potassium secretion by four mechanisms:
1. sodium-potassium ATPase pump, causing
potassium to diffuse across the luminal
membrane into the tubule.
2. increases the potassium gradient from the renal
interstitial fluid to the interior of the epithelial
cell, which reduces backleakage of potassium
ions from inside the cells.
3. synthesis of potassium channels.
4. stimulates aldosterone secretion by the adrenal
• Hypocalcemia increase the excitability of nerve and
muscle cells result in hypocalcemic tetany.
• Hypercalcemia depresses neuromuscular excitability
and can lead to cardiac arrhythmias.
A. 50 percent in the plasma = ionized form.
B. 40 percent = bound to the plasma proteins.
C. 10 percent = complexed in the non-ionized form
with anions such as phosphate and citrate.
• The usual rate of dietary calcium intake is about 1000
mg/day, with about 900 mg/day of calcium excreted
in the feces.
2- Control of renal calcium excretion and
extracellular calcium ion concentration:
A. 99 % stored in the bone.
B. 0.1 % in the extracellular fluid.
C. 1.0 % in the intracellular fluid and cell organelles.
• One of the most important regulators of bone uptake
and release of calcium is PTH.
• PTH regulates plasma calcium concentration
through three main effects:
(1) by stimulating bone resorption.
(2) by stimulating activation of vitamin D, which then
increases intestinal reabsorption of calcium.
(3) by directly increasing renal tubular calcium
• Renal calcium excretion = Calcium filtered –
• Normally, about 99 % of calcium is reabsorbed,
only 1% of calcium is excreted.
• Percentage of calcium reasbsorption:
1. 65% reabsorbed in the proximal tubule.
2. 25 to 30% is reabsorbed in the loop of Henle.
3. 4 to 9% is reabsorbed in the distal and collecting
• When less than 0.1 mmol/min amount of phosphate is
present in the glomerular filtrate, essentially all the filtered
phosphate is reabsorbed.
• When more than 0.1 mmol/min amount is present, the
excess is excreted.
• Most people ingest large quantities of phosphate in milk
products and meat.
• 75 to 80% is reabsorbed by proximal tube.
• 10 % is reabsorbed by distal tubule
• 1% are reabsorbed in the loop of Henle, collecting tubules,
and collecting ducts.
• 10% of the filtered phosphate is excreted in the urine.
3- regulation of renal phosphate excretion
• PTH can play a significant role in regulating
phosphate concentration through two effects:
(1) PTH promotes bone resorption, thereby dumping
large amounts of phosphate ions into the
extracellular fluid from the bone salts.
(2) PTH decreases the transport maximum for
phosphate by the renal tubules, so a greater
proportion of the tubular phosphate is lost in the
• Whenever plasma PTH is increased, tubular
phosphate reabsorption is decreased and more
phosphate is excreted.
• Phosphate enters the cell from the lumen by a
sodium-phosphate co-transporter and exits
the cell across the basolateral membrane by a
process that is not well understood.
• More than one half of the body’s magnesium is stored in the bones.
• Although the total plasma magnesium concentration is about 1.8 mEq/L,
more than one half of this is bound to plasma proteins.
• Therefore, the free ionized concentration of magnesium is only about
• The normal daily intake of magnesium is about 250 to 300 mg/day.
• Magnesium is involved in many biochemical processes in the body,
including activation of many enzymes, its concentration must be closely
• The following disturbances lead to increased magnesium excretion:
(1) Increased extracellular fluid magnesium concentration.
(2) Extracellular volume expansion.
(3) increased extracellular fluid calcium concentration.
4- Control of renal magnesium excretion and
extracellular magnesium ion concentration.
• Extracellular fluid volume is determined mainly by the
balance between intake and output of water and salt.
• Pressure diuresis: refers to the
effect of increased blood
pressure to raise urinary
• Pressure natriuresis: refers to
the rise in sodium excretion
that occurs with elevated
The Basic Renal–body Fluid
DISTRIBUTION OF EXTRACELLULAR FLUID
BETWEEN THE INTERSTITIAL SPACES AND
• Ingested fluid initially goes into the blood, but it
rapidly becomes distributed between the
interstitial spaces and the plasma.
• Accumulation of fluid in the interstitial spaces by
(1) increased capillary hydrostatic pressure.
(2) decreased plasma colloid osmotic pressure.
(3) increased permeability of the capillaries.
(4) obstruction of lymphatic vessels.
Role Of Hormones In Regulating
A) ROLE OF ANG II IN CONTROLLING RENAL EXCRETION:
• Increased levels of Ang II cause sodium and water
retention & also increase in arterial blood pressure.
• Decreased levels of Ang II cause sodium and water
excretion & also reduction in arterial blood pressure.
B) ROLE OF ALDOSTERONE IN CONTROLLING RENAL
• Increased levels of Aldosterone cause sodium and water
reabsorption + secretion of potassium.
• Decreased levels of Aldosterone cause sodium and water
excretion + reabsorption of potassium.
C) ROLE OF ADH IN CONTROLLING RENAL WATER
• Increased level of ADH causes reabsorption of water and
excretion large amount of Sodium and increase arterial
• Decreased level of ADH causes decreased reabsorption of
water and excretion small amount of Sodium and slightly
decreased arterial pressure.
D) ROLE OF ATRIAL NATRIURETIC PEPTIDE IN CONTROLLING
• Increased level of ANP causes increased excretion of salt
• Decreased level of ANP causes decreased excretion of salt
• Conditions That Cause Large Increases In Blood Volume
And Extracellular Fluid Volume:
1. Heart diseases.
2. Increased capacity of circulation (pregnancy & varicose
vein in leg).
• Conditions That Cause Large Increases In Extracellular
Fluid Volume But With Normal Blood Volume:
1. Nephrotic syndrome—loss of plasma proteins in urine and
sodium retention by the kidneys
2. Liver cirrhosis—decreased synthesis of plasma proteins by
the liver and sodium retention by the kidneys.