Control of Renal Calcium Excretion and Extracellular Calcium Ion Concentration The total calcium in the plasma 5 mEq/L Ca ion activates the sliding filament

mechanism and essential factor in blood clotting

About 50 per cent of the plasma calcium is ionized, with the remainder being bound to the plasma proteins or complexed with anions such as phosphate

About 50 per cent of the plasma calcium can be filtered at the glomerulus

When calcium ion concentration falls to low levels (hypocalcemia), the excitability of nerve and muscle cells increases markedly and can in extreme cases result in hypocalcemic tetany

Hypercalcemia depresses neuromuscular excitability and can lead to cardiac arrhythmias

One of the most important regulators of bone uptake and release of calcium is PTH

The parathyroid glands are directly stimulated by the low calcium levels to promote increased secretion of PTH

PTH regulates plasma calcium concentration through

(1) by stimulating bone resorption (2) by stimulating activation of vitamin D

in the kidneys (3) by directly increasing renal tubular

calcium reabsorption

Compensatory responses to decreased plasma ionized calcium concentration mediated by parathyroid hormone and vitamin D

Factors that alter renal calcium excretion

↓ Calcium Excretion ↑ Calcium Excretion

↑Parathyroid hormone (PTH) ↓PTH

↓Extracellular fluid volume ↑Extracellular fluid volume

↓Blood pressure ↑Blood pressure

↑Plasma phosphate ↓Plasma phosphate

Vitamin D3  

Phosphate excretion by the kidneys Plasma phosphate concentration is usually maintained at

about 4 mEq/L

The renal tubules have a normal transport maximum for reabsorbing phosphate of about 0.1 mM/min

Parathyroid hormone regulate phosphate concentration through:(1) PTH promotes bone resorption, thus 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 that a greater proportion of the tubular phosphate is lost in the urine

Integration of Renal Mechanisms for Control of Extracellular Fluid

Extracellular fluid volume is determined mainly by the balance between intake and output of water and salt

When ADH-Thirst mechanisms are functioning normally a change in the amount of sodium chloride in the extracellular fluid is matched by a similar change in the amount of extracellular water, so that osmolarity and sodium concentration are maintained constant

Sodium Excretion Is Controlled by Altering Glomerular Filtration or Tubular Sodium Reabsorption Rates

The two variables that influence sodium and water excretion are the rates of filtration and the rates of reabsorption:

Excretion = Glomerular filtration – tubular reabsorption

GFR normally is about 180 L/day, tubular reabsorption is 178.5 L/day, and urine excretion is 1.5 L/day

Tubular reabsorption and GFR usually are regulated precisely, so that excretion by the kidneys can be exactly matched to intake of water and electrolytes

If the kidneys become greatly vasodilated and GFR increases, this raises sodium chloride delivery to the tubules, which in turn leads to

(1) increased tubular reabsorption of much of the extra sodium chloride filtered, called glomerulotubular balance

(2) macula densa feedback, in which increased sodium chloride delivery to the distal tubule causes afferent arteriolar constriction and return of GFR toward normal

Neither of these two mechanisms operates perfectly to restore distal sodium chloride delivery back to normal

When this happens other feedback mechanisms such as changes in blood pressure and changes in various hormones, that eventually return sodium excretion to equal sodium intake

Importance of Pressure Natriuresis and Pressure Diuresis in Maintaining Body Sodium and Fluid Balance

One of the mechanisms for control of blood volume and extracellular fluid volume, as well as for the maintenance of sodium and fluid balance, is the effect of blood pressure on sodium and water excretion-called the pressure natriuresis and pressure diuresis mechanisms, respectively.

Pressure diuresis refers to the effect of increased blood pressure to raise urinary volume excretion

Pressure natriuresis refers to the rise in sodium excretion that occurs with elevated blood pressure

Pressure Natriuresis and Diuresis Are Key Components of a Renal-Body Fluid Feedback for Regulating Body Fluid Volumes and Arterial Pressure

The extracellular fluid volume, blood volume, cardiac output, arterial pressure, and urine output are all controlled at the same time as separate parts of this basic feedback mechanism

This feedback mechanism helps to maintain fluid balance and to minimize changes in blood volume, extracellular fluid volume, and arterial pressure as follows:

1. An increase in fluid intake above the level of urine output causes a temporary accumulation of fluid in the body

2. As long as fluid intake exceeds urine output, fluid accumulates in the blood and interstitial spaces, causing parallel increases in blood volume and extracellular fluid volume

3. An increase in blood volume raises mean circulatory filling pressure

4. An increase in mean circulatory filling pressure raises the pressure gradient for venous return

5. An increased pressure gradient for venous return elevates cardiac output

6. An increased cardiac output raises arterial pressure

7. An increased arterial pressure increases

urine output by way of pressure diuresis8. The increased fluid excretion

balances the increased intake, and further accumulation of fluid is prevented

The renal-body fluid feedback mechanism operates to prevent continuous accumulation of salt and water in the body during increased salt and water intake

As long as kidney function is normal and the pressure diuresis mechanism is operating effectively, large changes in salt and water intake can be accommodated with only slight changes in blood volume, extracellular fluid volume, cardiac output, and arterial pressure

Sympathetic Nervous System Control of Renal Excretion

Changes in sympathetic activity can alter renal sodium and water excretion as well as regulation of extracellular fluid volume under some conditions

When blood volume is reduced by hemorrhage, the pressures in the pulmonary blood vessels decrease causing activation of the sympathetic nervous system

Effects of increases renal sympathetic nerve activity

(1) constriction of the renal arterioles, with resultant decreased GFR(2) increased tubular reabsorption of salt and water(3) stimulation of renin release and increased angiotensin II and aldosterone formation, both of which further increase tubular reabsorption

Sympathetic Nervous System Control of Renal Excretion

Role of Angiotensin II In Controlling Renal Excretion

When sodium intake is elevated above normal, renin secretion is decreased, causing decreased angiotensin II formation, thus increasing the kidneys' excretion of sodium and water

The net result is to minimize the rise in extracellular fluid volume and arterial pressure that would otherwise occur when sodium intake increases

Changes in activity of the renin-angiotensin system act as a powerful amplifier of the pressure natriuresis mechanism for maintaining stable blood pressures and body fluid volumes.

Role of Aldosterone in Controlling Renal Excretion

Aldosterone increases sodium reabsorption, especially in the cortical collecting tubules

The increased sodium reabsorption is also associated with increased water reabsorption and potassium secretion

The net effect of aldosterone is to make the kidneys retain sodium and water but to increase potassium excretion in the urine

The function of aldosterone in regulating sodium balance is closely related to that of angiotensin II

Reduction in sodium intake, the increased angiotensin II levels that occur stimulate aldosterone secretion, which in turn contributes to the reduction in urinary sodium excretion and, therefore, to the maintenance of sodium balance

Role of Aldosterone in Controlling Renal Excretion

Role of ADH in Controlling Renal Water Excretion

High levels of ADH increase water reabsorption by the kidneys and help to minimize the decreases in extracellular fluid volume and arterial pressure that would otherwise occur

Water deprivation for 24 to 48 hours normally causes only a small decrease in extracellular fluid volume and arterial pressure. If the effects of ADH are blocked with a drug that antagonizes the action of ADH, the same period of water deprivation causes a substantial fall in both extracellular fluid volume and arterial pressure

Role of ADH in Controlling Renal Water Excretion

Role of Atrial Natriuretic Peptide in Controlling Renal Excretion

Atrial natriuretic peptide (ANP), released by the cardiac atrial muscle fibers

The stimulus for release of this peptide is overstretch of the atria, which can result from excess blood volume

ANP cause small increases in GFR and decreases in sodium reabsorption by the collecting ducts

These combined actions of ANP lead to increased excretion of salt and water, which helps to compensate for the excess blood volume

Role of Atrial Natriuretic Peptide in Controlling Renal Excretion