RENAL RENAL REGULATION OF K+, Ca++, P04++ AND Mg++:
INTEGRATION OF RENAL MECHANISMS FOR CONTROL OF BLOOD
VOLUME AND EXTRACELLULAR FLUID VOLUME:
CHAPTER 30 Physiology
Regulation of K+ Excretion and K+ concentration in Extracellular Fluid
(ECF)
▪ 4.2 mEq/L(0.3 mEq/L) extracellular fluid potassium
concentration
▪ Many cell functions are sensitive to changes in
concentration.
▪ Increase of 3 to 4 mEq/L causes cardiac arrhythmias,
higher conc. Leads to cardiac arrest or fibrillation.
▪ 98% total potassium is contained in cells and 2% in ECF.
▪ Can serve as an overflow site for excess extracellular fluid K
during hyperkalemia or source of K during hypokalemia.
▪ Redistribution of K+ between intra and ECF compartments
provides the first line of defense against changes in ECF K+
conc.
▪ Daily intake ranges between 50 and 200 mEq/day.
▪ Failure to rapidly rid the extracellular fluid of K+ could
cause life-threatening hyperkalemia.
▪ Loss of K+ in ECF could cause severe hypokalemia.
▪ Maintenance of K+ depends primarily on excretion by
kidneys. Amount excreted in feces is only about 5 to 10%.
Regulation of Internal K+ Distribution
▪ K+ ECF would rise to lethal level if ingested K+ did not
rapidly move into the cell.
▪ Most of the ingested K+ rapidly moves into the cells until
kidneys can eliminate the excess.
Factors that alter K distribution between the ICF and ECF
Factors that shift K into cells Factors that shift K out of cells
(Decrease extracellular K+) (Increase Extracellular K+)
Insulin Insulin Deficiency (diabetes
Aldosterone mellitus)
β-adrenergic stimulation Aldosterone def (Addison’s dss)
Alkalosis β-adrenergic blockade
Acidosis
Cell lysis
Strenuous exercise
Increased ECF osmolarity
Acidosis
Overview of Renal Potassium Excretion
❖ Insulin stimulates K+ uptake into cells.
▪ K excretion is determined by 3 renal processes
▪ In people who have insulin def owing to DM, rise
in plasma K+ conc after eating a meal is much
greater than normal.
▪ Injection of insulin, helps to correct
hyperkalemia.
▪ 756 mEq/day is the normal rate of K filtration; constant
❖ Aldosterone Increases K uptake into cells
▪ Increased K intake also stimulates secretion of
▪ 65 % is reabsorbed in proximal tubule. 25 to 30%
aldosterone, which increases cell K uptake.
▪ Excess aldosterone secretion (Conn’s syndrome)
is associated with hypokalemia, due to
▪ Sites of K+ excretion: 1) principal cells of late distal tubule
movement of extracellular K+ into the cells.
▪ Patients with deficient aldosterone production
(Addison’s dss) then have hyperkalemia due to
accumulation of K+ in ECF.
❖ β-Adrenergic Stimulation increases cellular uptake of K+
▪ increased secretion of epinephrine
(catecholamine) can cause movement of K+ from
ECF to ICF mainly by activation of β-Adrenergic
receptors.
▪ Propranolol (β-Adrenergic receptors) used for
treatment of hypertension, causes K+ to move
out of the cells and creates a tendency toward
hyperkalemia.
❖ Acid-Base Abnormalities can cause changes in K+
distribution
▪ Metabolic acidosis increases extracellular K
conc., causing loss of K from cells, whereas
metabolic alkalosis decreased ECF K+ conc.
▪ Increased H+ conc is to reduce activity of Na+-K+
adenosine triphosphate (ATPase) pump. This
decreases cellular uptake of K+ and raises ECF K+.
❖ Cell lysis causes increased ECF K+ concentration.
▪ Large amounts of K contained in cells are
released into ECF when cells are destroyed.
▪ Causes significant hyperkalemia if large amounts
of tissue are destroyed as occurs with severe
muscle injury or RBC lysis.
❖ Strenuous Exercise can cause hyperkalemia by releasing K
from Skeletal muscle
▪ Prolonged exercise causes K+ to be release from
skeletal muscle into ECF.
▪ Mild but clinically significant after heavy exercise
in patients treated with β-Adrenergic blockers or
individuals with insulin deficiency.
❖ Increased ECF osmolarity causes redistribution of K+ from
cells to ECF
▪ Increased ECF osmolarity causes osmotic flow of
water out of cells.
▪ Cellular dehydration increases intracellular K+
conc., thereby promoting diffusion of K out of
cells and increasing ECF K+ conc.
▪ In DM, large increases in plasma glucose raise
ECF osmolarity, causing cell dehydration and
movement of K+ from cells into ECF.
1) Rate of K filtration (GFR multiplied by plasma
K conc)
2) Rate of K reabsorption by tubules
3) Rate of K secretion by tubules
because of autoregulation mechanisms for GF.
reabsorbed in a loop of Henle (thick ascending) where K+ is
actively co-transported along with Na+ and Cl-.
2) cortical collecting tubules.
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 ▪ With high K+ intakes, increase K+ secretion into distal and
collecting tubules. Can exceed the amount of K+ in GFR,
indicating a powerful mechanism for secreting K+.
▪ If K+ intake is low, secretion rate also decreases. With
extreme reductions, net reabsorption of K+ in distal
segments of nephron and K+ excretion fall to 1% of K+ in
the GFR.
Potassium Secretion by Principal Cells of Late Distal and Cortical
collecting Tubules
▪ Principal cells make up about 90% of epithelial cells.
▪ Luminal membrane of the cell is highly permeable to K+.
▪ Secretion of K+ from blood into tubular lumen is a two step
process:
(1) Na+-K+ ATPase pump- found in the basolateral
membrane. Initiates the uptake from the interstitium into
the cell. Moves Na out of cell into interstitium and at the
same time moves potassium to the interior of the cell.
(2) Passive diffusion- from the interior of cell into tubular
fluid. Na+-K+ ATPase pump creates a high intracellular K+
conc, which provides the driving force for passive diffusion.
▪ Control of K secretion by Principal Cells. Primary factors
are
1) Activity of Na+-K+ ATPase pump
2) Electrochemical gradient
3) Permeability of luminal membrane for K+.
▪ Intercalated Cells can Reabsorb K during depletion. H-K
ATPase transport mechanism is located in the luminal
membrane.
Summary of Factors that Regulate K secretion:
▪ Most important factors that stimulate K secretion by
principal cells
1) Increased ECF K+ conc
o 3 mechanisms:
1) Stimulates Na+ -K+ ATPase pump, increases K +
uptake across basolateral membrane. Which
then Increases ICF K+ causes K+ to diffuse across
the luminal membrane into the tubule.
2) Increases K+ gradient from renal interstitial
fluid to interior of epithelial cell; reduces back
leakage of K+ from inside cells through
basolateral membrane.
3)Stimulates Aldosterone secretion by adrenal
cortex
2) increased aldosterone
o Aldosterone stimulates active reabsorption of Na
ions by principal cells of late distal tubules and
collecting ducts.
o This is mediated by Na-K ATPase pump that
transports Na outward and pumps K into the cell
(same with 1). Powerful effect to control rate of
K secretion.
o 2nd effect, increase permeability of luminal
membrane for K+, further adding to effectiveness
of aldosterone.
o Increased extracellular K ion concentration
stimulates aldosterone secretion. Therefore
increases potassium excretion by the kidneys
then reduces ECF K+ conc back toward normal.
3) Increased tubular flow rate.
o Rise in distal tubular flow rate (volume
expansion, high Na+ intake) stimulates K+
secretion
o Effect of high-volume flow: increase luminal conc
of K+ reduces the driving force for K diffusion
across the luminal membrane. With increased
tubular flow rate, secretion of K is continuously
flushed down the tubule, so rise in tubular K+
conc becomes minimized. Net potassium
secretion is stimulated by increased tubular flow
rate.
o With high Na+ intake, there is decreased
aldosterone secretion, that decreases the rate of
K secretion, therefore reducing urinary excretion
of potassium.
o Two effects of high Na+ intake, counterbalances
each other . With low Na+intake, there is little
change in K+ excretion because of
counterbalancing effects of increased
aldosterone secretion and decreased tubular
flow rate on potassium secretion.
▪ H+ ion concentration (acidosis) decreases potassium
secretion
o Decreasing H ion concentration (alkalosis)
increases K+ secretion.
o Primary mechanism is by reducing the activity of
the Na+-K+ ATPase pump. This in turn decreases
intracellular potassium concentration and
subsequent passive diffusion of K+ across the
luminal membrane into the tubule.
o Prolonged acidosis increases urinary K+ secretion,
due to inhibition of proximal tubular NaCl and
water reabsorption which increases distal
volume delivery, thereby stimulating secretion of
K+. This overrides the inhibitory effect of H+ ions
on the Na+-K+ ATPase pump.
o Chronic acidosis leads to loss of potassium
o Acute acidosis leads to decreased potassium
excretion.
Control of Renal Calcium Excretion and Extracellular Calcium Ion
Concentration
▪ Ca++ concentration remains tightly controlled at 2.4 mEq/L.
▪ When it falls to low levels (hypocalcemia), excitability of
nerve and muscle cells increases markedly and can result
in hypocalcemic tetany. This is characterized by spastic
skeletal muscle contractions.
▪ Hypercalcemia depresses neuromuscular excitability and
leads to cardiac arrhythmias.
▪ 50% of total calcium in the plasma (5 mEq/L)m exists in
ionized form. Has biological activity at cell membranes.
▪ Remainder is bound to plasma proteins (40% ) or
complexed in non-ionized form with anions such as
phosphate and citrate (10%).
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 ▪ Acidosis, less Ca++ bound to plasma proteins. Alkalosis,
greater amount of Ca++ bound to plasma proteins.
Therefore, Px with alkalosis are more susceptible to
hypocalcemic tetany.
▪ Large share of Ca excretion occurs in feces.
▪ Usual rate of Ca++ intake 1000mg/day, with about 900
mg/day of Ca++ excreted in feces. Fecal calcium excretion
can exceed Ca++ ingestion because Ca can also be secreted
into intestinal lumen. GI tract and the regulatory
mechanisms play a major role in Ca++ homeostasis.
▪ Ca++ in the body (99%) stored in bone, with about 1% in
ECF and 0.1% in ICF. Bone is a large reservoir for storing
Ca++ and source of Ca++ when ECF conc tends to decrease.
▪ Parathyroid hormone(PTH), one of most important
regulators of bone uptake. When Ca++ conc falls below
normal, parathyroid glands are directly stimulated by low
Ca++ levels to promote increased secretion of PTH. It then
acts directly on bones to increase resorption of bone salts,
to release large amounts of calcium into the ECF.
▪ When Ca++ ion is elevated, PTH secretion decreases, no
bone resorption, excess Ca++ is deposited in bones because
of new bone formation. Bones, do not have an
inexhaustible supply of Ca. Therefore, over long term,
intake of Ca++ must be balanced with Ca++ excretion by GF
tract and kidneys.
▪ With increased PTH, increase C++a reabsorption in thick
ascending loops of Henle and distal tubules, which reduces
urinary excretion of Ca++.
Control of Ca++ Excretion by the Kidneys
▪ Ca++ is both filtered and reabsorbed in kidneys but not
secreted.
▪ Renal Ca excretion=Ca++ filtered-Ca++ reabsorbed
▪ About 50% of Ca is ionized, with remainder bound to
plasma proteins or complexes with anions such as P04.
▪ Only about 50% of plasma Ca can be filtered by
glomerulus.
▪ Normally 99% of filtered Ca is reabsorbed by tubules with
only about 1% being excreted. 65% of filtered Ca++ is
reabsorbed in proximal tubule, 25 to 30% is reabsorbed in
loop of Henle, and 4 to 9% is reabsorbed in distal and
collecting tubules. Similar to Na.
▪ Phosphate also influences Ca++ reabsorption. Increase in
plasma phosphate stimulates PTH, which increases Ca++
reabsorption by renal tubules, thereby reducing Ca++
excretion.
▪ Ca reabsorption is also stimulated by metabolic acidosis
and inhibited by metabolic alkalosis.
Factors that Alter Renal Calcium Excretion
Decrease Calcium Excretion Increase Calcium Excretion
Increase PTH Decrease PTH
Decrease ECF volume Increase ECF volume
Decrease BP Increase BP
Increase Plasma phosphate Decrease Plasma phosphate
Metabolic acidosis Metabolic Alkalosis
Vitamin D3
Regulation of Renal Phosphate Excretion
▪ Excretion in kidneys is controlled by an overflow
mechanism.
▪ Renal tubules have a normal transport maximum for
reabsorbing phosphate of about 0.1 mM/min.
▪ When less than this amount is present, essentially all
filtered phosphate is reabsorbed. When more than this is
present, the excess is excreted.
▪ Phosphate normally begins to spill into urine when
concentration in the ECF rises above threshold of about 0.8
mM/L. Most people ingest large quantities of phosphate
in milk products and meat, therefore concentration of
phosphate is usually maintained above 1mM/L, a level at
which there is continual excretion of phosphate into the
urine.
▪ Tubular phosphate reabsorption can also influence
phosphate excretion.
▪ PTH can play a significant role in regulating phosphate
concentration through two effects
1) PTH promotes bone resorption, diming
large amounts of phosphate ions into the
ECF from bone salts
2) PTC decreases the transport max for
phosphate by renal tubules, greater
proportion of tubular phosphate is lost in
urine. Thus, whenever plasma PTH is
increased, tubular phosphate reabsorption
is decreased and more phosphate is
excreted.
Control of Renal Mg Excretion and Extracellular Mg ion
Concentration
▪ More than half of the body's Mg+ is stored in bones. Rest
resides within cells. Less than 1% located in ECF.
▪ Total plasma Mg+ conc. Is 1.8 mEq/L, more than one half is
bound to plasma proteins. Free ionized conc of Mg+ is only
about 0.8 mEq/L.
▪ 250-300 mg/day normal daily intake of Mg+, only half of
this intake is absorbed by GI. The kidneys normally excrete
about 10 to 15% of Mg+ in glomerular filtrate.
▪ Renal excretion of Mg can increase during Mg+ excess or
decrease to almost nil during Mg+ depletion.
▪ Regulation is achieved mainly by changing tubular
reabsorption. The proximal tubule usually reabsorbs only
about 25% of filtered Mg. Primary site of reabsorption in
loop of Henle, about 65% of filtered load of Mg+ is
reabsorbed. Only a small amount (<5%) is reabsorbed in
distal and collecting tubules.
▪ Disturbances that lead to increased Mg excretion\
1) Increased ECF Mg+ conc
2) Extracellular volume expansion
3) Increased ECF Ca++ conc
Integration of Renal Mechanism for Control of ECF
▪ ECF volume is determined mainly by balance between
intake and output of water and salt. It is dictated by
person’s habits rather than by physiologic control
mechanisms
▪ Antidiuretic hormone(ADH)- thirst mechanisms
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Sodium Excretion is Precisely Matched to intake Under Steady State
▪ Under steady-state conditions, excretion of electrolytes by
kidneys is determined by intake.
▪ If disturbances of kidney function are not too severe, Na
balance may be achieved mainly by intrarenal adjustments
with minimal changes in ECF volume or other systemic
adjustments.
▪ But when perturbations to kidneys, severe and intrarenal
compensations are exhausted, systemic adjustments must
be invoked, such as changes in blood pressure, changes in
circulating hormones and alterations of SNS activity.
▪ These compensations are necessary, because a sustained
imbalance between fluid and electrolyte intake and
excretion would quickly lead to accumulation or loss of
electrolytes and fluid causing cardiovascular collapse.
Sodium Excretion is controlled by Altering Glomerular Filtration or
Tubular Sodium Reabsorption Rates
▪ Excretion=Glomerular Filtration-Tubular reabsorption
▪ GFR normally is about 190 L/day, tubular reabsorption is
178.5 L/day, urine excretion is 1,5 L/day
▪ Small changes in GFR or tubular reabsorption potentially
can cause large changes in renal excretion.
▪ Even with disturbances that alter GFR or tubular
reabsorption, changes in urinary excretion are minimized
by various buffering mechanisms.
▪ When kidneys are vasodilated and GFR increases, this
raised NaCl delivery to tubules, which leads to two
intrarenal compensations
1) Increased tubular reabsorption of much of
extra NaCl filtered called glomerulotubular
balance
2) Macula densa feedback, increased NaCl
delivery to distal tubule causes afferent
arteriolar constriction and return of GFR
toward normal.
Importance of Pressure Natriuresis and Pressure Diuresis in
Maintaining Body Na and Fluid Balance
▪ Pressure diuresis, refers to effect of increased BP to raise
urinary volume excretion
▪ Pressure Natriuresis, refers to the rise in Na excretion that
occurs with elevated BP.
▪ Because both usually occur in parallel, these were referred
to as pressure natriuresis
▪ Most basic and powerful mechanism for control of blood
volume and ECF volume, as well as maintenance of Na
fluid balance.
▪ Acute increase in BP causes a twofold to threefold increase
in urinary sodium output. This effect is independent of
changes in activity of the SNS or of various hormones, such
as angiotensin II, ADH, or aldosterone.
▪ With chronic increase in BP, effectiveness of pressure
natriuresis is greatly enhanced because the increased BD
also after a short time delay, suppresses renin release,
therefore, decreases formation of angiotensin I I and
aldosterone.
▪ Angiotensin II and aldosterone, inhibit renal tubular
reabsorption of Na, thereby amplifying the direct effects of
increased BP to raise Na and water excretion.
Pressure Natriuresis and Diuresis are key components of a
Renal-Body Fluid Feedback for Regulating Body Fluid Volumes and
Arterial Pressure
▪ 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.
▪ Feedback mechanisms helps to maintain fluid balance as
follows
▪ Increase in fluid intake above the level of urine output
causes a temporary accumulation of fluid in the body🡪
As long as fluid intake exceeds urine output, fluid
accumulates in the blood and interstitial spaces,
causing parallel increase in blood volume and ECF
volume🡪raises mean circulatory filling
pressure🡪pressure raises the pressure gradient for
venous return🡪elevates cardiac output🡪 raises arterial
pressure🡪increases urine output by way of pressure
dieresis. Only slight increase in BP is required to raise
urinary excretion several fold🡪? balances the
increased intake and further accumulation of fluid is
prevented.
▪ Renal-body fluid feedback mechanism operates to prevent
continuous accumulation of salt and water in the body
during increased salt and water intake.
▪ When fluid intake falls below normal, there is a tendency
toward deceased blood volume and ECF volume, as well as
reduced arterial pressure. Even a small decrease in BP
causes a large decrease in urine output.
Precision of Blood Volume and ECF volume and ECF volume
Regulation
▪ Blood remains almost exactly constant despite extreme
changes in daily fluid intake. The reason for this is the ff:
1) slight change in blood volume causes a
marked change in cardiac output
2) a slight change in cardiac output causes a
large change in BP.
3) Slight change in blood causes a large change
in urine output
Distribution of ECF between interstitial spaces and vascular system
▪ Blood volume and ECF volume are usually controlled in
parallel with each other.
▪ Ingested fluid initially goes into the blood, but it rapidly
becomes distributed between the interstitial spaces and
plasma.
▪ Principal factors that can cause accumulation of fluid in the
interstitial spaces include
1) increased capillary hydrostatic pressure
2) Decreased plasma colloid osmotic pressure
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 3) Increased permeability of the capillaries
4) Obstruction of lymphatic vessels
▪ When small amounts of fluid accumulate in the blood, as a
result of either too much fluid intake or a decrease in renal
output of fluid, about 20 to 30% of it stays in the blood and
increases the blood volume. Remainder is distributed to
the interstitial spaces. When ECF volume rises more than
30-50% above normal, all the additional fluid goes into
interstitial spaces and little remains in the blood. Once
interstitial fluid pressure rises from its normally negative
value to become positive, tissue interstitial spaces become
compliant and large amounts of fluid then pour into the
tissues without interstitial fluid pressure rising much more.
▪ Under normal conditions, interstitial spaces act as an
overflow reservoir for excess fluid, causing an increase in
volume 10-30 liters. This causes edema. It also acts to
protect the CVS against dangerous overload that could
lead to pulmonary edema and cardiac failure.
▪ ECF volume and blood volume are controlled
simultaneously but distribution between interstitium and
blood depend on physical properties of the circulation and
as well as on dynamics of fluid exchange through capillary
membrane.
Nervous and Hormonal Factor Increase the Effectiveness of
Renal-Body Fluid Feedback Control
▪ Nervous and hormonal mechanisms usually act in concert
with pressure natriuresis and pressure dieresis
mechanisms making them more effective in minimizing
changes in blood volume, ECF volume and arterial
pressure.
Sympathetic Nervous System Control of Renal Excretion: Arterial
Baroreceptor and Low-Pressure Stretch Receptor Reflex
▪ When blood volume is reduced by hemorrhage, pressure
in pulmonary blood vessels and other low-pressure regions
of the thorax decrease, causing reflex activation of SNS.
This increases renal sympathetic nerve activity, which has
several effects to decrease sodium and water excretion
1) Constriction of the renal arterioles, with resultant
decreased GFR
2) Increases tubular reabsorption of salt and water
3) Stimulation of renin release and increased
angiotensin II and aldosterone formation
▪ Further activation of SNS occurs because of a decreased
stretch of arterial baroreceptors located in the carotid
sinus and aortic arch. Plays an important role in rapid
restitution of blood volume in hemorrhage.
Role of Angiotensin II in Controlling Renal Excretion
▪ Angiotensin II, powerful controllers of Na excretion
▪ When Na+ intake is elevated above normal, renin secretion
is decreased, causing decreased angiotensin II formation,
decreases tubular reabsorption of sodium and water, thus
increasing the kidney’s excretion of Na and water.
▪ Net result is to minimize rise in ECF volume and arterial
pressure.
▪ In hypertensive patients( high angiotensin II curve) who
have impaired ability to decrease renin secretion, pressure
natriuresis curve is not as steep. Therefore, when Na+
intake is raised, much greater increases in arterial pressure
are needed to increase sNa+ excretion and maintain Na+
balance.
▪ When angiotensin II formation is blocked with an
angiotensin-converting enzyme inhibitor or an angiotensin
II receptor antagonist, the renal-pressure natriuresis curve
is shifted to a lower pressures; this indicated an enhanced
ability of the kidneys to excrete sodium because normal
levels of sodium excretion can now be maintained at
reduced arterial pressures.
▪ Excessive Angiotensin II does not cause large increases in
ECF volume because increased arterial pressure
counterbalances Angiotensin-mediated sodium retention.
Role of Aldosterone in Controlling Renal Excretion
▪ Aldosterone increases Na+ reabsorption, in cortical
collecting tubules. Net effect is to make kidneys retain Na
and water but increases K+ excretion in urine.
▪ With reduction in sodium intake, increased angiotensin II
stimulates aldosterone secretion, which contributes to the
reduction in urinary Na+ excretion.
▪ During Chronic Oversecretion of aldosterone, Kidneys
“escape” from Sodium Retention as Arterial Pressure Rises.
Primary reason for the escape is the pressure natriuresis
and diuresis that occur when arterial pressure rises.
▪ Conn’s syndrome, patients with tumors of the adrenal
gland that has excessive infusion or formation of
aldosterone
▪ Addison’s disease, patients with adrenal insufficiency has a
tendency toward low blood pressure and has increased
excretion of sodium and water.
▪ During water deprivation, ADH plasma levels elevate than
increase water reabsorption. When there is excess ECF
volume, decreased ADH levels reduce reabsorption of
water by kidneys, thus helping to rid the body of excess
volume.
▪ Excess ADH secretion usually causes only small increases in
ECF volume but large decrease in Na concentration. High
levels of ADH do not cause major increase of blood volume
or arterial pressure, although high ADH levels can cause
severe reduction in extracellular Na+ ion concentration.
Role of Atrial Natriuretic Peptide in Controlling Renal Excretion
▪ Atrial natriuretic peptide (ANP), natriuretic hormone
released by the cardiac atrial muscle fibers. Stimulus for
release of this peptide appears to be overstretch of the
atria, which can result from excess blood volume. Acts on
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 the kidneys to cause small increases in GFR and decreases
in Na+ reabsorption by collecting ducts.
▪ Excessive production of ANP or complete lack of ANP does
not cause major changes in blood volume because these
effects can easily be overcome by small changes in blood
pressure, acting through pressure natriuresis.
High Na intake Suppresses Antinatriuretic Systems and Activates
Natriuretic Systems
▪ Small increase in ECF volume triggers various mechanisms
in body to increase sodium excretion
1) Activation of low pressure receptor reflex that
originate from the stretch receptors of the right
atrium and the pulmonary blood vessels. They inhibit
sympathetic nerve activity to kidneys to decrease
tubular Na+reabsorption. Important in first few hours
or perhaps the first day after large intake of salt and
water
2) Small increases in arterial pressure through pressure
natriuresis
3) Suppression of angiotensin II formation caused by
increased arterial pressure and ECF volume
expansion, decreases tubular Na+ reabsorption by
eliminating the normal effect of angiotensin to
increase Na+reabsorption. Reduced angiotensin II also
decreases aldosterone secretion
4) Stimulation of the natriuretic system, especially ANP.
Conditions that cause Large Increases in Blood Volume and
Extracellular Fluid Volume
▪ Increased blood volume and extracellular fluid volume
caused by heart disease.
o In CHF, blood volume may increase 15-20% and
ECF volume sometimes increases by 200% or
more.
o Initially, heart failure reduces cardiac output,
consequently decreases arterial pressure,
activates multiple sodium-retaining systems,
especially the renin-angiotensin, aldosterone,
sympathetic nervous system. Low BP causes
kidneys to retain salt and water.
o In myocardial failure, heart valvular dss and
congenital abnormalities of the heart, an
important circulatory compensation is an
increase in blood volume, which helps to return
cardiac output and blood pressure to normal.
This allows even the weakened heart to maintain
a life-sustaining level of cardiac output.
▪ Increased blood volume caused by increased capacity of
circulation
o Increase in vascular capacity initially reduces
mean circulatory filling pressure, which leads to
decreased cardiac output and decreased arterial
pressure. Fall in pressure causes salt and water
retention until blood volume increases
sufficiently to fill the extra capacity.
Conditions that cause Large increase in ECF volume but with Normal
Blood Volume
▪ These are usually initiated by leakage of fluid and protein
into the interstitium which tends to decrease the blood
volume.
▪ Nephrotic Syndrome-Loss of plasma proteins in urine and
sodium retention by the kidneys
o One of most important clinical causes of edema
o Glomerular capillaries leak large amounts of
protein into the filtrate and urine because of
increased permeability. 30-50 gms can be lost in
a day. As a consequence, the plasma colloid
osmotic pressure falls to lower levels which in
turn causes edema and decreases plasma
volume.
o Renal Na+ retention occurs through multiple
mechanisms such as activation of the
renin-angiotensin system, aldosterone and
possibly SNS.
o Due to large amount of Na+ and water retention,
the plasma protein conc become further diluted,
causing more fluid to leak into tissues
▪ Liver cirrhosis-decreased synthesis of Plasma Proteins by
live and sodium retention by kidneys
o Similar to nephritic syndrome but reduction in
plasma protein concentration results from
destruction of liver cells, thus reducing the ability
of the liver to synthesize enough plasma
proteins.
o Also associated with large amounts of fibrous
tissue in liver structure, which greatly impedes
the flow of portal blood through the liver, in turn
raises capillary pressure throughout portal
vascular bed, which contributes to leakage of
fluid and proteins into peritoneal cavity, called
ascites.
o Kidneys continue to retain salt and water until
plasma volume and arterial pressure are restored
to normal.