Integration of Renal Mechanisms for Control of Blood
Increase in fluid intake above the level of urine
Volume & ECF Volume
Renal regulation of K+, Ca2+, PO4-, & Mg2+
CONTROL MECHANISMS FOR REGULATING SODIUM AND
WATER EXCRETION:
Extracellular fluid volume is determined mainly by
the balance between intake and output of water and
salt.
Under steady state conditions, excretion by the
kidneys is determined by intake.
To maintain life, a person must, over the long term,
excrete almost precisely the amount of sodium
ingested.
If disturbances of kidney function are not too severe,
sodium balance may be achieved mainly by inter-
renal adjustments with minimal changes in
extracellular fluid volume or other systemic
adjustments.
Sustained imbalance between sodium intake and
excretion would quickly lead to fluid accumulation or
fluid loss and cause cardiovascular collapse within a
few days.
Variables of Na+ Excretion
Glomerular filtration is normally about 180L/day
Tubular reabsorption is 178.5L/day
Urine Excretion is 1.5L/day
Excretion = Glomerular filtration tubular reabsorption
Tubular reabsorption & GFR usually are regulated
precisely, so that excretion by the kidneys can be
exactly matched to intake of water and electrolytes.
BUFFERING MECHANISM IN CASES WITH ALTERED GFR OR
TUBULAR REABSORPTION
Drugs or high fever cause kidneys to vasodilate and increase
GFR
Increase NaCl delivery to the tubules
2 Intrarenal Compensation:
1. Glomerulotubular balance increased tubular
reabsorption of the extra NaCl filtered.
2. Macula densa feedback increased NaCl delivery
to the distal tubule causes afferent arteriolar constriction and
return of GFR to normal.
PRESSURE NATRIURESIS AND PRESSURE DIURESIS IN
MAINTAINING BODY SODIUM AND FLUID BALANCE:
One of the most basic and powerful mechanisms for
control of blood volume and extracellular fluid
volume, as well as maintenance of sodium and fluid
balance, is the effect of blood pressure on Na & H2O
excretion.
Pressure diuresis effect of increased blood
pressure to raise urinary volume excretion.
Pressure natriuresis rise in sodium excretion that
occurs with elevated blood pressure.
Pressure Natriuresis & Diuresis - Key Components of a Renal-
Body
Fluid Volumes and Arterial Pressure
The effect of increased blood pressure to raise urine
output is part of a powerful feedback system that
operates to maintain balance between fluid intake
and output.
The extracellular fluid volume, blood volume, cardiac
output, arterial pressure, and urine output are all part of
the basic feedback mechanism.
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2.
output temporary accumulation of fluid in the
body.
3. Fluid intake exceeds urine output - fluid accumulates
in the blood and interstitial spaces, causing parallel
increases in blood volume and extracellular fluid
volume.
4. Increase in blood volume raises mean circulatory
filling pressure.
5. Increase in mean circulatory filling pressure raises
the pressure gradient for venous return.
6. Increased pressure gradient for venous return
elevates cardiac output.
7. Increased cardiac output raises arterial pressure.
8. Increased arterial pressure increases urine output by
way of pressure diuresis.
9. 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.
PRECISION OF BLOOD VOLUME AND EXTRACELLULAR FLUID
VOLUME REGULATION
Blood volume remains almost exactly constant
despite extreme changes in daily fluid intake.
Factors that provide effective feedback control of blood
volume:
1. Slight change in blood volume causes a marked
change in cardiac output
2. Slight change in cardiac output causes a large change
in blood pressure
3. Slight change in blood pressure causes a large
change in urine output.
DISTRIBUTION OF EXTRACELLULAR FLUID BETWEEN THE
INTERSTITIAL SPACES AND VASCULAR SYSTEM
Ingested fluid initially goes into the blood, but it
rapidly becomes distributed between the interstitial
spaces and the plasma.
Principal factors that can cause accumulation of fluid
in the interstitial spaces:
1. Increased capillary hydrostatic pressure
2. Decreased plasma colloid osmotic pressure
3. Increased permeability of the capillaries
4. Obstruction of lymphatic vessels
Excess fluid intake - 20-30% stays in blood and the rest
goes to interstitial spaces, due to compliance of
interstitial space tissue.
NERVOUS AND HORMONAL FACTORS INCREASE THE
EFFECTIVENESS OF RENAL-BODY FLUID FEEDBACK CONTROL
Sympathetic Nervous System control of Renal Excretion:
Reduced Blood Volume
Decrease pressure in pulmonary vessels
Decrease Sodium and Water Excretion
1. Constriction of renal arterioles decreased GFR
2. Increased tubular reabsorption of salt and water
3. Stimulation of renin release & increased angiotensin II &
aldosterone
ROLE OF ANGIOTENSIN II IN CONTROLLING RENAL
EXCRETION:
One of the bodys most powerful controllers of
sodium excretion

Increase Sodium Intake
decreased renin & Angiotensin II
decreased tubular reabsorption of sodium
increase excretion of sodium & water
decreased extracellular fluid & arterial pressure
When the angiotensin control of natriuresis is fully
functional, the pressure natriuresis is steep,
indicating that only minor changes in blood pressure
are needed to increase sodium excretion when
sodium intake is raised.
In some hypertensive patients, angiotensin levels
cannot be decreased in response to increased
sodium intake because they have impaired ability to
decrease renin secretion.
With ACE-I or ARB blockade an enhanced ability of
the kidneys to
Excrete sodium is noted because normal levels of
sodium excretion can
Now be maintained at reduced arterial pressures.
Excessive Angiotensin II does not cause large
increases in extracellular Fluid volume because
increased arterial pressure counterbalances
Angiotensin-mediated sodium retention.
ROLE OF ALDOSTERONE IN CONTROLLING RENAL EXCRETION
ALDOSTERONE:
increases sodium reabsorption in cortical collecting
tubules
increase water reabsorption & Potassium secretion
During chronic oversecretion of Aldosterone, in patients
with Conns syndrome there is only transient increase in
sodium reabsorption & decreased sodium excretion.
After 1-3 days when the arterial pressure rises
sufficiently, the kidneys escape from the sodium and
water retention and thereafter excrete amounts of
sodium equal to the daily intake.
The primary reason for the escape is the pressure
natriuresis & diuresis
ROLE OF ADH IN CONTROLLING RENAL WATER EXCRETION
Water Deficit ADH production water reabsorption
Minimize the decrease in extracellular fluid volume and
arterial pressure
Excess ADH secretion usually cause only small increases
in extracellular fluid volume but large decreases in
sodium concentration
ROLE OF ATRIAL NATRIURETIC PEPTIDE IN CONTROLLING
RENAL EXCRETION
ATRIAL NATRIURETIC PEPTIDE:
released by the cardiac atrial muscle fibers
Excess Blood Volume
Overstretch of the Atria
Small increase in GFR
Decreases Sodium reabsorption by CD
Increased excretion of salt & water
INTEGRATED RESPONSES TO CHANGES IN SODIUM INTAKE
High Sodium intake suppresses Antinatriuretic
Systems & activates Natriuretic Systems.
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1. Activation of low pressure receptor
reflexes inhibit sympathetic nerve activity
to the kidneys to decrease tubular sodium
reabsorption.
2. Small increases in arterial pressure raise
sodium excretion through pressure
natriuresis.
3. Suppression of Angiotensin II formation
decrease tubular sodium reabsorption
4. Stimulation of Natriuretic Systems ANP
cause further increase in sodium excretion.
CONDITIONS THAT CAUSE LARGE INCREASES IN BLOOD
VOLUME AND EXTRACELLULAR FLUID VOLUME
A. Congestive Heart Failure/CHD:
reduced cardiac output
decreased arterial pressure
activate multiple sodium-retaining systems
(Renin-angiotensin, Aldosterone, Sympathetic Nervous
System)
Retain Salt & Water
CONDITIONS THAT CAUSE LARGE INCREASES IN ECF VOLUME
BUT WITH NORMAL BLOOD VOLUME
A. NEPHROTIC SYNDROME:
Loss of plasma protein in the urine due to increased
permeability of the glomerulus.
Plasma colloid osmotic pressure falls to low levels
Cause the capillaries all over the body to filter large amounts
of fluid into the various tissues causing edema & decrease the
plasma volume.
Activation of various sodium retaining systems
Net result: MASSIVE FLUID RETENTION
B. LIVER CIRRHOSIS:
Reduction in plasma protein concentration due to destruction
of liver cells
Fibrous tissue in the liver impedes flow of portal blood
through the liver
Raise capillary pressure throughout the portal vascular bed
Salt & Water retention
REGULATION OF POTASSIUM EXCRETION AND POTASSIUM
CONCENTRATION IN THE EXTRACELLULAR FLUID
Extracellular fluid potassium concentration normally
is regulated precisely at about 4.2mEq/L.
Over 98% of total body potassium is contained in the
cells and only 2% in Extracellular fluid.
Maintenance of normal potassium balance depends
primarily on excretion By the kidneys, only 5-10% is
excreted via the feces.
Control of potassium distribution between the
extracellular and intracellularCompartments also
plays an important role in potassium homeostasis.
Redistribution of potassium between the intra and
extracellular fluid compartments provides a first line
of defense against changes in extracellular fluid
potassium concentration.
REGULATION OF INTERNAL POTASSIUM DISTRIBUTION:
 Factors that can alter Potassium Distribution between the
Intra and Extracellular Fluid:
Factors that shift K+ into the Cells (decreased
extracellular K+)
1. Insulin
2. Aldosterone
3. B-adrenergic stimulation
4. Alkalosis
Factors that shift K+ out of the cells (increased
extracellular K+)
1. Insulin deficiency (diabetes Mellitus)
2. Aldosterone deficiency
3. B-adrenergic blockade
4. Acidosis
5. Cell lysis
6. Strenuous exercise
Overview of Renal Potassium Excretion:
Potassium excretion is determined by the sum of three
processes:
1. Rate of potassium filtration
2. Rate of potassium reabsorption
3. Rate of potassium secretion by the tubules
65% of filtered potassium is reabsorbed in the proximal
tubule
25-30% of the filtered potassium is reabsorbed in the
Loop of Henle
The most important sites for regulating potassium
excretion are the distal tubules and cortical collecting
tubules, where potassium can be either reabsorbed or
secreted, depending on the needs of the body.
Potassium Secretion in the Principal Cells of the Late Distal
and Cortical Collecting Tubules
2 Step process of Potassium Secretion:
1. Uptake from the interstitium into the cells by the
sodium potassium ATPase pump in the basolateral
membrane of the cell. Moves Na+ out and K+ inside
the cell.
2. Passive diffusion of potassium from the interior of
the cell into the tubular fluid.
Primary Factors that control Potassium secretion by the
Principal Cells:
1. Activity of the Na-K ATPase pump
2. Electrochemical gradient for potassium secretion
from the blood to the tubular lumen
3. Permeability of the luminal membrane for potassium
Intercalated cells can reabsorb potassium during
potassium depletion thru the hydrogen-potassium
ATPase transport mechanism located in the luminal
membrane. This transporter reabsorbs potassium in
exchange for hydrogen ion necessary during potassium
depletion but plays a small role during normal conditions.
The most important factors that stimulate potassium
secretion by the principal cells:
1. Increased extracellular fluid potassium concentration
2. Increased aldosterone
3. Increased tubular flow rate
Almost all the calcium in the body (99%) is stored in the
bone, 1% in the extracellular fluid, 0.1% in the
intracellular fluid
One of the most important regulators of bone uptake and
release of Calcium is PTH
FACTORS THAT ALTER RENAL CALCIUM EXCRETION:
Calcium Excretion Calcium Excretion
PTH PTH
Extracellular fluid volume Extracellular fluid volume
Blood Pressure Blood Pressure
Plasma phosphate Plasma phosphate
Metabolic acidosis Metabolic alkalosis
Vitamin D3
REGULATION OF RENAL PHOSPHATE EXCRETION
Phosphate excretion by the kidneys is controlled
primarily by an overflow mechanism:
When less phosphate is present, essentially all the
filtered phosphate is reabsorbed, when more, the excess
is excreted.
PTH plays a significant role in regulating phosphate
concentration thru 2 effects:
1. PTH promotes bone resorption, dumping large
amounts of phosphate ions in the extracellular fluid
2. PTH decreases the transport maximum for
phosphate by the renal tubules, greater proportion is
lost in urine.
CONTROL OF RENAL MAGNESIUM EXCRETION AND
EXTRACELLULAR MAGNESIUM ION CONCENTRATION
More than one half of the bodys magnesium is stored in
the bones; most of the rest resides within the cells
Renal excretion of magnesium can increase markedly
during magnesium excess or decrease to almost nil
during magnesium depletion.
The primary site of reabsorption is the loop of Henle
Increase Magnesium excretion:
1. Increased extracellular fluid magnesium
concentration
2. Extracellular volume expansion
3. Increased extracellular fluid calcium concentration

CONTROL OF RENAL CALCIUM EXCRETION AND

EXTRACELLULAR CALCIUM ION CONCENTRATION:
HYPOCALCEMIA- increase excitability of nerve & muscle
- spastic skeletal muscle contractions
HYPERCALCEMIA - depresses neuromuscular excitability
- lead to cardiac arrythmias
About 50% of the total calcium exists in the ionized form
The remainder is either bound to plasma proteins or
complexed to non-ionized form
In acidosis, less calcium is bound to plasma proteins. In
alkalosis calcium is bound therefore more susceptible to
hypocalcemic tetany.
A large share of calcium excretion occurs in the feces.
The gastrointestinal tract and the regulatory mechanisms
that influence intestinal calcium absorption and secretion
play a major role in calcium homeostasis.
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