Chapter 30: Renal Regulation of Potassium, Calcium, Phosphate, and Magnesium;

Integration of Renal Mechanisms for Control of Blood Volume and ECF Volume ❖ Insulin stimulates K+ uptake into cells.
▪ In people who have insulin def owing to DM, rise in plasma K+ conc after
Regulation of K+ Excretion and K+ concentration in Extracellular Fluid (ECF) eating a meal is much greater than normal.
▪ Injection of insulin, helps to correct hyperkalemia.
▪ 4.2 mEq/L(0.3 mEq/L) extracellular fluid potassium concentration
❖ Aldosterone Increases K uptake into cells
▪ Many cell functions are sensitive to changes in concentration.
▪ Increased K intake also stimulates secretion of aldosterone, which
▪ Increase of 3 to 4 mEq/L causes cardiac arrhythmias, higher conc. Leads to cardiac
increases cell K uptake.
arrest or fibrillation.
▪ Excess aldosterone secretion (Conn’s syndrome) is associated with
▪ 98% total potassium is contained in cells and 2% in ECF.
hypokalemia, due to movement of extracellular K+ into the cells.
▪ Can serves as an overflow site for excess extracellular fluid K during hyperkalemia
▪ Patients with deficient aldosterone production (Addison’s dss) of then has
or source of K during hypokalemia.
hyperkalemia due to accumulation of K+ in ECF.
▪ Redistribution of K+ between intra and ECF compartments provides first line of
defense against changes in ECF K+ conc.
❖ β-Adrenergic Stimulation increases cellular uptake of K+
▪ Daily intake ranges between 50 and 200 mEq/day.
▪ increase secretion of epinephrine (catecholamine) can cause movement
▪ Failure to rapidly rid the extracellular fluid of K+ could cause life-threatening
of K+ from ECF to ICF mainly by activation of β-Adrenergic receptors.
hyperkalemia.
▪ Propranolol (β-Adrenergic receptors) used for treatment of hypertension,
▪ Loss of K+ in ECF could cause severe hypokalemia.
causes K+ to move out of the cells and creates a tendency toward
▪ Maintenance of K+ depends primarily on excretion by kidneys. Amount excreted in
hyperkalemia.
feces is only about 5 to 10%.
❖ Acid-Base Abnormalities can cause changes in K + distribution
Regulation of Internal K+ Distribution
▪ Metabolic acidosis increases extracellular K conc., causing loss of K from
▪ K+ ECF would rise to lethal level if ingested K+ did not rapidly move into the cell.
cells, whereas metabolic alkalosis decreases ECF K+ conc.
▪ Most of the ingested K+ rapidly moves into the cells until kidneys can eliminate the
▪ Increased H+ conc is to reduce activity of Na+-K+ adenosine triphosphate
excess.
(ATPase) pump. This decreases cellular uptake of K+ and raises ECF K+.
❖ Cell lysis causes increased ECF K+ concentration.
Factors that alter K distribution between the ICF and ECF
▪ Large amounts of K contained in cells are released into ECF when cells
Factors that shift K into cells Factors that shift K out of cells are destroyed.
(Decrease extracellular K+) (Increase Extracellular K+) ▪ Causes significant hyperkalemia if large amounts of tissue are destroyed
Insulin Insulin Deficiency (diabetes mellitus) as occurs with severe muscle injury or RBC lysis.
Aldosterone Aldosterone def (Addison’s dss) ❖ Strenuous Exercise can cause hyperkalemia by releasing K from Skeletal muscle
β-adrenergic stimulation β-adrenergic blockade ▪ Prolonged exercise causes K+ to be release from skeletal muscle into
Alkalosis Acidosis ECF.
Cell lysis ▪ Mild but clinically significant after heavy exercise in patients treated with
Strenuous exercise β-Adrenergic blockers or individuals with insulin deficiency.
Increased ECF osmolarity ❖ Increased ECF osmolarity causes redistribution of K+ from cells to ECF
Acidosis ▪ Increased ECF osmolarity causes osmotic flow of water out of cells.
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 ▪ Cellular dehydration increases intracellular K+ conc., thereby promoting
diffusion of K out of cells and increasing ECF K+ conc.
▪ In DM, large increase in plasma glucose raise ECF osmolarity, causing
cell dehydration and movement of K+ from cells into ECF.
Overview of Renal Potassium Excretion
▪ K excretion is determined by 3 renal processes
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
▪ 756 mEq/day is the normal rate of K filtration; constant because of autoregulation
mechanisms for GF.
▪ 65 % is reabsorbed in proximal tubule. 25 to 30% reabsorbed in the loop of Henle
(thick ascending) where K+ is actively co-transported along with Na+ and Cl-.
▪ Sites of K+ excretion: 1) principal cells of late distal tubule 2) cortical collecting
tubules.
▪ With high K+ intakes, increase K+ secretion into distal and collecting tubules. Can
exceed the amount of K+ in GFR, indicating 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 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 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 responsible located in 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 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 Increase 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 increases
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.
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 o With high Na+ intake, there is decreased aldosterone secretion, that
decreases the rate of K secretion, therefore reduce 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 Decrease 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
increased markedly and can in result to hypocalcemic tetany. This is characterized
by spastic skeletal muscle contractions.
▪ Hypercalcemia depresses neuromuscular excitability and lead 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%).
▪ 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 body (99%) stored in bone, with about 1% in ECF and 0.1% in ICF. Bone is
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 increase 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 complex
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.
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 Factors that Alter Renal Calcium Excretion ▪ 250-300 mg/day normal daily intake of Mg+, only half of this intake is absorbed by
Decrease Calcium Excretion Increase Calcium Excretion GI. The kidneys normally excrete about 10 to 15% of Mg+ in glomerular filtrate.
Increase PTH Decrease PTH ▪ Renal excretion of Mg can increased during Mg+ excess or decrease to almost nil
Decrease ECF volume Increase ECF volume during Mg+ depletion.
Decrease BP Increase BP ▪ Regulation is achieved mainly by changing tubular reabsorption. The proximal
Increase Plasma phosphate Decrease Plasma phosphate tubule usually reabsorbs only about 25% of filtered Mg. Primary site of reabsorption
Metabolic acidosis Metabolic Alkalosis in loop of Henle, about 65% of filtered load of Mg+ is reabsorbed. Only small amount
Vitamin D3 (<5%) is reabsorbed in distal and collecting tubules.
▪ Disturbances that lead to increased Mg excretion\
1) Increased ECF Mg+ conc
Regulation of Renal Phosphate Excretion 2) Extracellular volume expansion
▪ Excretion in kidneys is controlled by an overflow mechanism. 3) Increased ECF Ca++ conc
▪ Renal tubules have a normal transport maximum for reabsorbing phosphate of
about 0.1 mM/min. Integration of Renal Mechanism for Control of ECF
▪ When less than this amount is present, essentially all filtered phosphate is ▪ ECF volume is determined mainly by balance between intake and output of water
reabsorbed. When more than this is present, the excess is excreted. and salt. It is dictated by person’s habits rather than by physiologic control
▪ Phosphate normally begins to spill into urine when concentration in the ECF rises mechanisms
above threshold of about 0.8 mM/L. Most people ingest large quantities of ▪ Antidiuretic hormone(ADH)- thirst mechanisms
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 Sodium Excretion is Precisely Matched to intake Under Steady State
phosphate into the urine. ▪ Under steady-state conditions, excretion of electrolytes by kidneys is determined by
▪ Tubular phosphate reabsorption can also influence phosphate excretion. intake.
▪ PTH can play a significant role in regulating phosphate concentration through two ▪ If disturbances of kidney function are not too severe, Na balance may be achieved
effects mainly by intrarenal adjustments with minimal changes in ECF volume or other
1) PTH promotes bone resorption, diming large amounts of phosphate systemic adjustments.
ions into the ECF from bone salts ▪ But when perturbations to kidneys, severe and intrarenal compensations are
2) PTC decreases the transport max for phosphate by renal tubules, exhausted, systemic adjustments must be invoked, such as changes in blood
greater proportion of tubular phosphate is lost in urine. Thus, pressure, changes in circulating hormones and alterations of SNS activity.
whenever plasma PTH is increased, tubular phosphate reabsorption ▪ These compensations are necessary, because a sustained imbalance between fluid
is decreased and more phosphate is excreted. and electrolyte intake and excretion would quickly lead to accumulation or loss of
electrolytes and fluid causing cardiovascular collapse.
Control of Renal Mg Excretion and Extracellular Mg ion Concentration
▪ More than half of body’s Mg+ is stored in bones. Rest resides within cells. Less than Sodium Excretion is controlled by Altering Glomerular Filtration or Tubular Sodium
1% located in ECF. Reabsorption Rates
▪ Total plasma Mg+ conc. Is 1.8 mEq/L, more than one half is bound to plasma ▪ Excretion=Glomerular Filtration-Tubular reabsorption
proteins. Free ionized conc of Mg+ is only about 0.8 mEq/L. ▪ GFR normally is about 190 L/day, tubular reabsorption is 178.5 L/day, urine
excretion is 1,5 L/day
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 ▪ 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 cause 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 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) 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
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
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 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 mechanism 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 rennin release and increased angiotensin II and aldosterone
formation
▪ Further activation of SNS occurs because of decreases 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, rennin 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 rennin 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 stimulate 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 dieresis 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 tendency toward low
blood pressure has increased excretion of sodium and water.
▪ During water deprivation, ADH plasma levels elevates 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
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 atria, which can result from excess blood volume. Acts on 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 Supppresses 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 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
increased by 200% or more.
o Initially, heart failure reduces cardiac output, consequently decreases
arterial pressure, activates multiple sodium-retaining systems, especially
the rennin-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 leaks 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 decrease plasma volume.
o Renal Na+ retention occurs through multiple mechanisms such as
activation of 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 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 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.
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