Chapter 27
Fluid, Electrolyte, and Acid-Base Balance
Body Water Content
Infants
have low body fat, low bone mass, and are 73% or more water
Total
water content declines throughout life
Healthy
males are about 60% water; healthy females are around 50%
This
difference reflects females:
Higher
body fat
Smaller
amount of skeletal muscle
In old
age, only about 45% of body weight is water
Fluid Compartments
Water
occupies two main fluid compartments
Intracellular
fluid (ICF) about two thirds by volume, contained in cells
Extracellular
fluid (ECF) consists of two major subdivisions
Plasma
the fluid portion of the blood
Interstitial
fluid (IF) fluid in spaces between cells
Other ECF lymph, cerebrospinal fluid,
eye humors, synovial fluid, serous fluid, and gastrointestinal secretions
Composition of Body Fluids
Water is
the universal solvent
Solutes
are broadly classified into:
Electrolytes
inorganic salts, all acids and bases, and some proteins
Nonelectrolytes
examples include glucose, lipids, creatinine, and urea
Electrolytes
have greater osmotic power than nonelectrolytes
Water
moves according to osmotic gradients
Electrolyte Concentration
Expressed
in milliequivalents per liter (mEq/L), a measure of the number of electrical
charges in one liter of solution
mEq/L =
(concentration of ion in [mg/L]/the atomic weight of ion) ΄ number of electrical charges on one ion
For single
charged ions, 1 mEq = 1 mOsm
For
bivalent ions, 1 mEq = 1/2 mOsm
Extracellular and Intracellular Fluids
Each fluid
compartment of the body has a distinctive pattern of electrolytes
Extracellular
fluids are similar (except for the high protein content of plasma)
Sodium is
the chief cation
Chloride
is the major anion
Intracellular
fluids have low sodium and chloride
Potassium
is the chief cation
Phosphate is the chief anion
Sodium and
potassium concentrations in extra- and intracellular fluids are nearly
opposites
This
reflects the activity of cellular ATP-dependent sodium-potassium pumps
Electrolytes
determine the chemical and physical reactions of fluids
Proteins,
phospholipids, cholesterol, and neutral fats account for:
90% of the
mass of solutes in plasma
60% of the
mass of solutes in interstitial fluid
97% of the mass of solutes in the
intracellular compartment
Fluid Movement Among Compartments
Compartmental
exchange is regulated by osmotic and hydrostatic pressures
Net
leakage of fluid from the blood is picked up by lymphatic vessels and returned
to the bloodstream
Exchanges
between interstitial and intracellular fluids are complex due to the selective
permeability of the cellular membranes
Two-way
water flow is substantial
Extracellular and Intracellular Fluids
Ion fluxes
are restricted and move selectively by active transport
Nutrients,
respiratory gases, and wastes move unidirectionally
Plasma is
the only fluid that circulates throughout the body and links external and
internal environments
Osmolalities of all body fluids are
equal; changes in solute concentrations are quickly followed by osmotic changes
Water Balance
To remain
properly hydrated, water intake must equal water output
Water
intake sources
Ingested
fluid (60%) and solid food (30%)
Metabolic
water or water of oxidation (10%)
Water
output:
Urine
(60%) and feces (4%)
Insensible
losses (28%), sweat (8%)
Increases in plasma osmolality trigger
thirst and release of antidiuretic hormone (ADH)
Regulation of Water Intake
The
hypothalamic thirst center is stimulated by:
Decreases
in plasma volume of 10%
Increases
in plasma osmolality of 1-2%
Thirst is
quenched as soon as we begin to drink water
Feedback
signals that inhibit the thirst centers include:
Damping of
mucosa of the mouth
Moistening
of the throat
Activation of stomach and intestinal
stretch receptors
Regulation of Water Output
Obligatory
water losses include:
Insensible
water losses from lungs and skin
Water that
accompanies undigested food residues in feces
Obligatory
water loss reflects the facts that:
Kidneys
excrete 900-1200 mOsm of solutes to maintain blood homeostasis
Urine
solutes must be flushed out of the body in water
Disorders of Water Balance: Dehydration
Water loss
exceeds water intake and the body is in negative fluid balance
Causes
include: hemorrhage, severe burns, prolonged vomiting or diarrhea, profuse
sweating, water deprivation, and diuretic abuse
Signs and
symptoms: cottonmouth, thirst, dry flushed skin, and oliguria
Prolonged
dehydration may lead to weight loss, fever, and mental confusion
Other consequences include hypovolemic
shock and loss of electrolytes
Disorders of Water Balance: Hypotonic
Hydration
Renal
insufficiency or an extraordinary amount of water ingested quickly can lead to
cellular overhydration, or water intoxication
ECF is
diluted sodium content is normal but excess water is present
The
resulting hyponatremia promotes net osmosis into tissue cells, causing swelling
These events must be quickly reversed to
prevent severe metabolic disturbances, particularly in neurons
Disorders of Water Balance: Edema
Atypical
accumulation of fluid in the interstitial space, leading to tissue swelling
Caused by
anything that increases flow of fluids out of the bloodstream or hinders their
return
Factors
that accelerate fluid loss include:
Increased
blood pressure, capillary permeability
Incompetent
venous valves, localized blood vessel blockage
Congestive
heart failure, hypertension, high blood volume
Edema
Hindered
fluid return usually reflects an imbalance in colloid osmotic pressures
Hypoproteinemia
low levels of plasma proteins
Forces
fluids out of capillary beds at the arterial ends
Fluids
fail to return at the venous ends
Results from protein malnutrition, liver
disease, or glomerulonephritis
Blocked
(or surgically removed) lymph vessels:
Cause
leaked proteins to accumulate in interstitial fluid
Exert
increasing colloid osmotic pressure, which draws fluid from the blood
Interstitial
fluid accumulation results in low blood pressure and severely impaired
circulation
Electrolyte Balance
Electrolytes
are salts, acids, and bases, but electrolyte balance usually refers only to
salt balance
Salts are
important for:
Neuromuscular
excitability
Secretory
activity
Membrane
permeability
Controlling
fluid movements
Salts
enter the body by ingestion and are lost via perspiration, feces, and urine
Sodium in Fluid and
Electrolyte Balance
Sodium
holds a central position in fluid and electrolyte balance
Sodium
salts:
Account
for 90-95% of all solutes in the ECF
Contribute
280 mOsm of the total 300 mOsm ECF solute concentration
Sodium is the
single most abundant cation in the ECF
Sodium is the only cation exerting
significant osmotic pressure
The role
of sodium in controlling ECF volume and water distribution in the body is a
result of:
Sodium
being the only cation to exert significant osmotic pressure
Sodium
ions leaking into cells and being pumped out against their electrochemical
gradient
Sodium concentration in the ECF normally
remains stable
Changes in
plasma sodium levels affect:
Plasma
volume, blood pressure
ICF and
interstitial fluid volumes
Renal
acid-base control mechanisms are coupled to sodium ion transport
Regulation of
Sodium Balance: Aldosterone
Sodium
reabsorption
65% of
sodium in filtrate is reabsorbed in the proximal tubules
25% is
reclaimed in the loops of Henle
When
aldosterone levels are high, all remaining Na+ is actively
reabsorbed
Water
follows sodium if tubule permeability has been increased with ADH
Regulation of
Sodium Balance: Aldosterone
The
renin-angiotensin mechanism triggers the release of aldosterone
This is
mediated by the juxtaglomerular apparatus, which releases renin in response to:
Sympathetic
nervous system stimulation
Decreased
filtrate osmolality
Decreased
stretch (due to decreased blood pressure)
Renin catalyzes the production of
angiotensin II, which prompts aldosterone release
Adrenal
cortical cells are directly stimulated to release aldosterone by elevated K+
levels in the ECF
Aldosterone
brings about its effects (diminished urine output and increased blood volume)
slowly
Cardiovascular System
Baroreceptors
Baroreceptors
alert the brain of increases in blood volume (hence increased blood pressure)
Sympathetic
nervous system impulses to the kidneys decline
Afferent
arterioles dilate
Glomerular
filtration rate rises
Sodium and water output increase
This
phenomenon, called pressure diuresis, decreases blood pressure
Drops in
systemic blood pressure lead to opposite actions and systemic blood pressure
increases
Since
sodium ion concentration determines fluid volume, baroreceptors can be viewed
as sodium receptors
Influence and Regulation of ADH
Water
reabsorption in collecting ducts is proportional to ADH release
Low ADH
levels produce dilute urine and reduced volume of body fluids
High ADH
levels produce concentrated urine
Hypothalamic
osmoreceptors trigger or inhibit ADH release
Factors that specifically trigger ADH
release include prolonged fever; excessive sweating, vomiting, or diarrhea;
severe blood loss; and traumatic burns
Atrial Natriuretic Peptide (ANP)
Reduces
blood pressure and blood volume by inhibiting:
Events
that promote vasoconstriction
Na+
and water retention
Is
released in the heart atria as a response to stretch (elevated blood pressure)
Has potent
diuretic and natriuretic effects
Promotes
excretion of sodium and water
Inhibits angiotensin II production
Influence
of Other Hormones on Sodium Balance
Estrogens:
Enhance
NaCl reabsorption by renal tubules
May cause
water retention during menstrual cycles
Are
responsible for edema during pregnancy
Progesterone:
Decreases
sodium reabsorption
Acts as a
diuretic, promoting sodium and water loss
Glucocorticoids
enhance reabsorption of sodium and promote edema
Regulation of Potassium
Balance
Relative
ICF-ECF potassium ion concentration affects a cells resting membrane potential
Excessive
ECF potassium decreases membrane potential
Too little K+ causes hyperpolarization
and nonresponsiveness
Hyperkalemia
and hypokalemia can:
Disrupt
electrical conduction in the heart
Lead to
sudden death
Hydrogen
ions shift in and out of cells
Leads to
corresponding shifts in potassium in the opposite direction
Interferes
with activity of excitable cells
Regulatory Site: Cortical Collecting
Ducts
Less than
15% of filtered K+ is lost to urine regardless of need
K+
balance is controlled in the cortical collecting ducts by changing the amount
of potassium secreted into filtrate
Excessive
K+ is excreted over basal levels by cortical collecting ducts
When K+
levels are low, the amount of secretion and excretion is kept to a minimum
Type A
intercalated cells can reabsorb some K+ left in the filtrate
Influence of
Plasma Potassium Concentration
High K+
content of ECF favors principal cells to secrete K+
Low K+
or accelerated K+ loss depresses its secretion by the collecting
ducts
Influence of Aldosterone
Aldosterone
stimulates potassium ion secretion by principal cells
In
cortical collecting ducts, for each Na+ reabsorbed, a K+
is secreted
Increased
K+ in the ECF around the adrenal cortex causes:
Release of
aldosterone
Potassium
secretion
Potassium
controls its own ECF concentration via feedback regulation of aldosterone
release
Regulation of Calcium
Ionic
calcium in ECF is important for:
Blood
clotting
Cell
membrane permeability
Secretory
behavior
Hypocalcemia:
Increases
excitability
Causes muscle tetany
Hypercalcemia:
Inhibits
neurons and muscle cells
May cause
heart arrhythmias
Calcium
balance is controlled by parathyroid hormone (PTH) and calcitonin
Regulation of Calcium and
Phosphate
PTH
promotes increase in calcium levels by targeting:
Bones
PTH activates osteoclasts to break down bone matrix
Small
intestine PTH enhances intestinal absorption of calcium
Kidneys
PTH enhances calcium reabsorption and decreases phosphate reabsorption
Calcium
reabsorption and phosphate excretion go hand in hand
Filtered
phosphate is actively reabsorbed in the proximal tubules
In the
absence of PTH, phosphate reabsorption is regulated by its transport maximum
and excesses are excreted in urine
High or
normal ECF calcium levels inhibit PTH secretion
Release of
calcium from bone is inhibited
Larger
amounts of calcium are lost in feces and urine
More
phosphate is retained
Influence of Calcitonin
Released
in response to rising blood calcium levels
Calcitonin
is a PTH antagonist, but its contribution to calcium and phosphate homeostasis
is minor to negligible
Regulation of Magnesium
Balance
Magnesium
is the second most abundant intracellular cation
Activates
coenzymes needed for carbohydrate and protein metabolism
Plays an
essential role in neurotransmission, cardiac function, and neuromuscular
activity
There is a
renal transport maximum for magnesium
Control
mechanisms are poorly understood
Regulation of Anions
Chloride
is the major anion accompanying sodium in the ECF
99% of
chloride is reabsorbed under normal pH conditions
When
acidosis occurs, fewer chloride ions are reabsorbed
Other
anions have transport maximums and excesses are excreted in urine
Acid-Base Balance
Normal pH
of body fluids
Arterial
blood is 7.4
Venous
blood and interstitial fluid is 7.35
Intracellular
fluid is 7.0
Alkalosis
or alkalemia arterial blood pH rises above 7.45
Acidosis
or acidemia arterial pH drops below 7.35 (physiological acidosis)
Sources of Hydrogen Ions
Most
hydrogen ions originate from cellular metabolism
Breakdown
of phosphorus-containing proteins releases phosphoric acid into the ECF
Anaerobic
respiration of glucose produces lactic acid
Fat
metabolism yields organic acids and ketone bodies
Transporting
carbon dioxide as bicarbonate releases hydrogen ions
Hydrogen Ion Regulation
Concentration
of hydrogen ions is regulated sequentially by:
Chemical
buffer systems act within seconds
The
respiratory center in the brain stem acts within 1-3 minutes
Renal
mechanisms require hours to days to effect pH changes
Chemical Buffer Systems
Strong
acids all their H+ is dissociated completely in water
Weak acids
dissociate partially in water and are efficient at preventing pH changes
Strong
bases dissociate easily in water and quickly tie up H+
Weak bases accept H+ more
slowly (e.g., HCO3― and NH3)
One or two
molecules that act to resist pH changes when strong acid or base is added
Three
major chemical buffer systems
Bicarbonate
buffer system
Phosphate
buffer system
Protein
buffer system
Any drifts
in pH are resisted by the entire chemical buffering system
Bicarbonate Buffer System
A mixture
of carbonic acid (H2CO3) and its salt, sodium bicarbonate
(NaHCO3) (potassium or magnesium bicarbonates work as well)
If strong
acid is added:
Hydrogen
ions released combine with the bicarbonate ions and form carbonic acid (a weak
acid)
The pH of the solution decreases only
slightly
If strong
base is added:
It reacts
with the carbonic acid to form sodium bicarbonate (a weak base)
The pH of
the solution rises only slightly
This
system is the only important ECF buffer
Phosphate Buffer System
Nearly
identical to the bicarbonate system
Its
components are:
Sodium
salts of dihydrogen phosphate (H2PO4―), a weak acid
Monohydrogen
phosphate (HPO42―), a weak base
This
system is an effective buffer in urine and intracellular fluid
Protein Buffer System
Plasma and
intracellular proteins are the bodys most plentiful and powerful buffers
Some amino
acids of proteins have:
Free
organic acid groups (weak acids)
Groups
that act as weak bases (e.g., amino groups)
Amphoteric
molecules are protein molecules that can function as both a weak acid and a
weak base
Physiological Buffer Systems
The
respiratory system regulation of acid-base balance is a physiological buffering
system
There is a
reversible equilibrium between:
Dissolved
carbon dioxide and water
Carbonic
acid and the hydrogen and bicarbonate ions
CO2 + H2O
« H2CO3 « H+ + HCO3―
During
carbon dioxide unloading, hydrogen ions are incorporated into water
When
hypercapnia or rising plasma H+ occurs:
Deeper and
more rapid breathing expels more carbon dioxide
Hydrogen
ion concentration is reduced
Alkalosis
causes slower, more shallow breathing, causing H+ to increase
Respiratory
system impairment causes acid-base imbalance (respiratory acidosis or
respiratory alkalosis)
Renal Mechanisms of Acid-Base
Balance
Chemical
buffers can tie up excess acids or bases, but they cannot eliminate them from
the body
The lungs
can eliminate carbonic acid by eliminating carbon dioxide
Only the
kidneys can rid the body of metabolic acids (phosphoric, uric, and lactic acids
and ketones) and prevent metabolic acidosis
The ultimate acid-base regulatory organs
are the kidneys
The most
important renal mechanisms for regulating acid-base balance are:
Conserving
(reabsorbing) or generating new bicarbonate ions
Excreting
bicarbonate ions
Losing a
bicarbonate ion is the same as gaining a hydrogen ion; reabsorbing a bicarbonate
ion is the same as losing a hydrogen ion
Hydrogen
ion secretion occurs in the PCT and in type A intercalated cells
Hydrogen
ions come from the dissociation of carbonic acid
Reabsorption of Bicarbonate
Carbon
dioxide combines with water in tubule cells, forming carbonic acid
Carbonic
acid splits into hydrogen ions and bicarbonate ions
For each
hydrogen ion secreted, a sodium ion and a bicarbonate ion are reabsorbed by the
PCT cells
Secreted hydrogen ions form carbonic
acid; thus, bicarbonate disappears from filtrate at the same rate that it
enters the peritubular capillary blood
Carbonic
acid formed in filtrate dissociates to release carbon dioxide and
water
Carbon
dioxide then diffuses into tubule cells, where it acts to trigger further
hydrogen ion secretion
Generating New Bicarbonate Ions
Two
mechanisms carried out by type A intercalated cells generate new bicarbonate
ions
Both
involve renal excretion of acid via secretion and excretion of hydrogen ions or
ammonium ions (NH4+)
Generating
New Bicarbonate Ions Using Hydrogen Ion Excretion
Dietary
hydrogen ions must be counteracted by generating new bicarbonate
The
excreted hydrogen ions must bind to buffers in the urine (phosphate buffer
system)
Intercalated
cells actively secrete hydrogen ions into urine, which is buffered and excreted
Bicarbonate
generated is:
Moved into
the interstitial space via a cotransport system
Passively
moved into the peritubular capillary blood
In
response to acidosis:
Kidneys
generate bicarbonate ions and add them to the blood
An equal amount of hydrogen ions are
added to the urine
This
method uses ammonium ions produced by the metabolism of glutamine in
PCT cells
Each
glutamine metabolized produces two ammonium ions and two bicarbonate ions
Bicarbonate moves to the blood and
ammonium ions are excreted in urine
Bicarbonate Ion Secretion
When the
body is in alkalosis, type B intercalated cells:
Exhibit
bicarbonate ion secretion
Reclaim
hydrogen ions and acidify the blood
The
mechanism is the opposite of type A intercalated cells and the bicarbonate ion
reabsorption process
Even
during alkalosis, the nephrons and collecting ducts excrete fewer bicarbonate
ions than they conserve
Respiratory Acidosis and
Alkalosis
Result
from failure of the respiratory system to balance pH
PCO2
is the single most important indicator of respiratory inadequacy
Normal PCO2
Fluctuates
between 35 and 45 mm Hg
Values
above 45 mm Hg signal respiratory acidosis
Values below 35 mm Hg indicate
respiratory alkalosis
Respiratory
acidosis is the most common cause of acid-base imbalance
Occurs
when a person breathes shallowly, or gas exchange is hampered by diseases such
as pneumonia, cystic fibrosis, or emphysema
Respiratory
alkalosis is a common result of hyperventilation
Metabolic Acidosis
All pH
imbalances except those caused by abnormal blood carbon dioxide levels
Metabolic
acid-base imbalance bicarbonate ion levels above or below normal (22-26
mEq/L)
Metabolic
acidosis is the second most common cause of acid-base imbalance
Typical
causes are ingestion of too much alcohol and excessive loss of bicarbonate ions
Other
causes include accumulation of lactic acid, shock, ketosis in diabetic crisis,
starvation, and kidney failure
Metabolic Alkalosis
Rising
blood pH and bicarbonate levels indicate metabolic alkalosis
Typical
causes are:
Vomiting
of the acid contents of the stomach
Intake of
excess base (e.g., from antacids)
Constipation,
in which excessive bicarbonate is reabsorbed
Respiratory and Renal
Compensations
Acid-base
imbalance due to inadequacy of a physiological buffer system is compensated for
by the other system
The
respiratory system will attempt to correct metabolic acid-base imbalances
The
kidneys will work to correct imbalances caused by respiratory disease
Respiratory Compensation
In
metabolic acidosis:
The rate
and depth of breathing are elevated
Blood pH
is below 7.35 and bicarbonate level is low
As carbon
dioxide is eliminated by the respiratory system, PCO2 falls below
normal
In
respiratory acidosis, the respiratory rate is often depressed and is the
immediate cause of the acidosis
In
metabolic alkalosis:
Compensation
exhibits slow, shallow breathing, allowing carbon dioxide to accumulate in the
blood
Correction
is revealed by:
High pH
(over 7.45) and elevated bicarbonate ion levels
Rising
PCO2
Renal Compensation
To correct
respiratory acid-base imbalance, renal mechanisms are stepped up
In
acidosis
High PCO2
and high bicarbonate levels
The high PCO2
is the cause of acidosis
The high
bicarbonate levels indicate the kidneys are retaining bicarbonate to offset the
acidosis
In
alkalosis
Low PCO2
and high pH
The
kidneys eliminate bicarbonate from the body by failing to reclaim it or by
actively secreting it
Developmental Aspects
Water
content of the body is greatest at birth (70-80%) and declines until adulthood,
when it is about 58%
At
puberty, sexual differences in body water content arise as males develop
greater muscle mass
Homeostatic
mechanisms slow down with age
Elders may
be unresponsive to thirst clues and are at risk of dehydration
The very
young and the very old are the most frequent victims of fluid, acid-base, and
electrolyte imbalances
Problems with
Fluid, Electrolyte, and Acid-Base Balance
Occur in
the young, reflecting:
Low
residual lung volume
High rate
of fluid intake and output
High
metabolic rate yielding more metabolic wastes
High rate
of insensible water loss
Inefficiency
of kidneys in infants