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Chapter 27
Fluid, Electrolyte,
and Acid-Base
Homeostasis
Fluid Compartments

The fluid compartments of the body are all contained in
either the intracellular compartment or the
extracellular compartment

Intracellular fluid is all fluid contained inside cells,
and comprises 2/3 of all body fluids

Extracellular fluid is all fluid outside the cells. 1/3 of
all body fluid is contained in the extracellular
compartment
Copyright © John Wiley & Sons, Inc. All rights reserved.
Fluid Compartments





Intracellular fluid (ICF) – about two thirds by
volume
Extracellular fluid (ECF) – consists of:
Plasma
Interstitial fluid (IF) – fluid in tissue spaces
Other ECF – lymph, CSF, synovial fluid, serous fluid
etc.
Copyright © John Wiley & Sons, Inc. All rights reserved.
Fluid Compartments

Babies are more “wet”
than adults, with water
composing about 80%
of total body mass
Water makes up 55–80% of total body
mass (depending on age and sex)
Copyright © John Wiley & Sons, Inc. All rights reserved.
Composition of Body Fluids

Extracellular fluids (ECFs) are similar (except for the high
protein content of plasma)



Sodium is the chief cation, chloride is the major anion
Intracellular fluid

Potassium is the chief cation, phosphate is the chief anion

Three times protein content than plasma
Sodium and potassium concentrations in ECF & ICF are
opposite due:

Cell membrane Na+/ K+ ATPase pump
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Fluid movement between plasma &
interstitial fluid




Exchange occurs across capillary membranes
At the arterial end, net HP is more (fluid flows out)
At the venous end of a bed, net COP is more ( fluid
flows in)
Any leakage of fluid from the blood is picked up by
lymphatics & returned to the blood
HP
35
HP16
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Fluid movement between intracellular
fluid & interstitial fluid

Exchanges between IF & ICF occur across plasma
membrane- depend on membrane permeability

Water moves according to osmotic gradients; from
low osmolarity to high osmolarity (from more water
to less water)
Copyright © John Wiley & Sons, Inc. All rights reserved.
Fluid movement between compartments:
Fluid movement after fluid intake: when you drink water,
water enters your blood from the digestive system
plasma osmolarity decreases
Water moves out of plasma to become part of the interstitial
fluid, and then moves from the interstitial fluid into cells
Reverse when dehydrated
Copyright © John Wiley & Sons, Inc. All rights reserved.
Fluid Balance

Normal fluid intake is through:
l
Ingestion of liquids and moist foods (2300mL/day)
l
Metabolic synthesis of water during cellular
respiration and dehydration synthesis (200mL/day)

Normal fluid loss is through:
l
The kidneys (1500mL/day)
l
Evaporation from the skin (600mL/day)
l
Exhalation from the lungs (300mL/day)
l
In the feces (100mL/day)
Copyright © John Wiley & Sons, Inc. All rights reserved.
Fluid Balance

Fluid intake and output (I & O) are usually balanced on
a daily basis, despite the fact that
intake of water and electrolytes
are rarely proportional
The kidneys excrete
excess water through
dilute urine, or retain water
through concentrated urine
Copyright © John Wiley & Sons, Inc. All rights reserved.
Regulation of water intake- the thirst
mechanism

The hypothalamic thirst center is stimulated:
By increases in plasma osmolarity- even a small increase (by
stimulating osmoreceptors in the hypothalamus)
thirst increases water intake – osmolarity becomes normal
decreased salivary secretions- sensory input relayed from
receptors in mucous membranes to thirst center
decreased blood pressure (significant decrease)
◦ renin released from kidney- in response angiotensin II is
formed which stimulates the thirst center
Copyright © John Wiley & Sons, Inc. All rights reserved.
Fluid Intake
Copyright © John Wiley & Sons, Inc. All rights reserved.
Regulation of Water Output



Antidiuretic hormone (ADH) plays a major role in directly
regulating water loss in the collecting ducts of the kidneys
Rise in osmolarity stimulates hypothalamic osmoreceptors triggers ADH release
Significant decrease in blood volume/BP also triggers ADH
release, but rise in osmolarity more potent stimulus
l
ADH increases permeability of the collecting ducts to
water by insertion of aquaporins into the principal cells –
water reabsorbed-producing a concentrated small volume
urine- water retained in the body
l
When ADH levels low- water in CDs not reabsorbed-
producing dilute urine
Copyright © John Wiley & Sons, Inc. All rights reserved.
Mechanisms and
Consequences of
ADH Release
Copyright © John Wiley & Sons, Inc. All rights reserved.
Regulation of Water Output
l
Water output also regulated by:
l
Aldosterone: promotes urinary Na+ reabsorption (followed
by water by osmosis) & decrease urine output
l
Atrial natriuretic peptide (ANP)
l
promotes excretion of Na+ followed by water excretionincreases urine output
l
Angiotensin II- decreases GFR- decreases urine output
Copyright © John Wiley & Sons, Inc. All rights reserved.
Edema

Edema occurs when excess interstitial fluid collects,
causing swelling in the tissues. Edema occurs anytime
filtration exceeds reabsorption

The most important causes of edema are:

increased blood pressure (increased blood hydrostatic
pressure)

an increase in the capillary permeability

a decrease in COP (decreased plasma proteins)

an obstruction in lymphatic drainage
Copyright © John Wiley & Sons, Inc. All rights reserved.
Electrolytes




Water is the universal solvent
Solutes classified into:
Nonelectrolytes –do not dissociate in solution e.g. glucose,
lipids, urea
Electrolytes –dissociate into ions in solution e.g. salts, acids,
bases
l
Electrolytes have greater osmotic power and cause fluid
shifts ( because more number of particles in solution)
l
Electrolytes expressed in milliequivalents per liter (mEq/L)
◦ Sodium - 136-146 mEq/L
◦ Potassium - 3.5-5.0 mEq/L
Copyright © John Wiley & Sons, Inc. All rights reserved.
Sodium

Most abundant extracellular cation
l accounts for most of osmolarity of ECF

Sodium salts account for 90-95% of all solutes in ECF

Regulation of Na-water balance is linked to BP &
blood volume regulation
Copyright © John Wiley & Sons, Inc. All rights reserved.
Regulation of Sodium Balance:
Aldosterone




Sodium reabsorption in the kidney
l
65% of sodium in filtrate is reabsorbed in the proximal
tubules
l
25% is reabsorbed in the loops of Henle
When aldosterone levels are high, all of remaining Na+ can be
reabsorbed in DCT & CDs-water follows if tubule
permeability has been increased with ADH
When aldosterone is inhibited- no more Na reabsorbed in
DCT & CDs
ANP: decreases Na reabsorption- causing sodium loss
followed by water loss in urine
Copyright © John Wiley & Sons, Inc. All rights reserved.
Chloride

Cl- is most prevalent extracellular anion

Regulation:
l
In the kidney negatively charged chloride passively
follows the positively charged Na+

Helps balance anions in different compartments e.g.
chloride shift across red blood cells with HCO3 ions

It plays a role in forming HCl in the stomach
Copyright © John Wiley & Sons, Inc. All rights reserved.
Potassium

K+ is the most abundant cation in intracellular fluid

Exchanged for H+ across cells to help regulate pH of
body fluids

Helps establish resting membrane potential & repolarize
nerve & muscle cells

Regulation: mainly by aldosterone which stimulates
principal cells to increase K+ secretion into the urine

Abnormal plasma K+ levels adversely affect cardiac and
neuromuscular function
Copyright © John Wiley & Sons, Inc. All rights reserved.
Clinical Application

Hyperkalemia- high K+ concentration
l
Can be caused by crush injury, hemolytic anemia's, (K+
released from ruptured cells)
l

Can cause death by abnormal cardiac rhythms
Hypokalemia- low K+ concentration
l
Can be caused by excessive vomiting, diarrhea
l
Nerve & muscle cells become less excitable, can cause
muscle paralysis
Copyright © John Wiley & Sons, Inc. All rights reserved.
Bicarbonate (HCO3-)

Forms the blood acid-base buffer system with carbonic acid.
l
Concentration increases as blood flows through systemic
capillaries due to CO2 released from metabolically active
cells
l
Concentration decreases as blood flows through pulmonary
capillaries and CO2 is exhaled

Kidneys are main regulator of plasma levels
l
Intercalated cells of collecting ducts generally reabsorb
HCO3-, but can excrete excess in the urine if levels high
Copyright © John Wiley & Sons, Inc. All rights reserved.
Calcium

98% located in bones and teeth.

Important role in blood clotting, neurotransmitter
release, muscle contraction

Regulated by parathyroid hormone:
l
1.Stimulates osteoclasts to release calcium from bone
l
2. Increases production of calcitriol (VitD)- which
promotes Ca++ absorption from GI tract
l
3.Increases reabsorption of Ca in kidneys
Copyright © John Wiley & Sons, Inc. All rights reserved.
Phosphate

Present as calcium phosphate salts in bones and teeth,
and in phospholipids, ATP, DNA and RNA

Is most important intracellular anion and acts as buffer of
H+ inside cells and in urine

Regulation: plasma levels are regulated by parathyroid
hormone
l resorption of bone releases phosphate
l in the kidney, PTH increase phosphate excretion,
lowering blood phosphate
l Calcitriol increases GI absorption of phosphate
Copyright © John Wiley & Sons, Inc. All rights reserved.
Clinical Application



Individuals at risk for fluid and electrolyte imbalances include:
those dependent on others for fluid and food needs
those undergoing medical treatment involving intravenous
infusions, drainage, suction, and urinary catheters

those receiving diuretics

individuals with burns, and those with altered states of
consciousness
Copyright © John Wiley & Sons, Inc. All rights reserved.
Acid-Base Balance

Normal pH of blood
l
Arterial blood is 7.4
l
Venous blood is 7.35

Alkalosis– arterial blood pH rises above 7.45

Acidosis– arterial pH drops below 7.35
Copyright © John Wiley & Sons, Inc. All rights reserved.
Sources of Acids

Produced from metabolic wastes:

e.g., lactic acid from anaerobic cellular respiration

e.g., phosphoric acid from nucleic acid metabolism

e.g. ketoacids from fat metabolism

Regulated by kidney through reabsorption and elimination of
HCO3- and H+

Volatile acid:

Carbonic acid produced when carbon dioxide combines with water
◦ CO2 + H2O  H2CO  H+ + HCO3l
Regulated by respiratory system through respiratory rate
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pH Regulation

Concentration of hydrogen ions in blood is regulated by:
l
Chemical buffer systems – act within seconds
l
The respiratory system– acts within 1-3 minutes
l
Renal mechanisms– require hours to days to effect pH
changes
Copyright © John Wiley & Sons, Inc. All rights reserved.

Strong acids – dissociate completely-
Chemical Buffer
Systems- General
Concepts
release all their H+ in water

Weak acids – dissociate partially in
water- act as buffers

Strong bases – dissociate easily in water
and quickly tie up H+

Weak bases – accept H+ more slowly
(e.g., HCO3¯)- act as buffers
Copyright © John Wiley & Sons, Inc. All rights reserved.
Chemical Buffer Systems

A chemical buffer consists of a weak acid and a weak
base

Resist pH changes when a strong acid or base is added by
converting strong acids or bases into weak acids & weak
bases

Three major chemical buffer systems
l
Bicarbonate buffer system
l
Phosphate buffer system
l
Protein buffer system
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Carbonic acid-Bicarbonate Buffer System

Bicarbonate buffer system is a mixture of carbonic
acid (H2CO3) a weak acid , and bicarbonate (HCO3 )


a weak base
This system is the most important ECF buffer (blood,
tissue fluids)
The HCO3 ion levels in ECF are regulated by the
kidney, the H2CO3 levels by the lungs
Copyright © John Wiley & Sons, Inc. All rights reserved.
Bicarbonate Buffer System- contd.

If there is an excess of H+ due to a strong acid the buffer
system acts by:
l
H+ released by strong acid combine with the HCO3 ions
to form carbonic acid; a weak acid which then replaces the
strong acid
H+ + HCO3¯
H2CO3
Therefore the pH of the solution decreases only slightly
If there is a shortage of H+ due to a strong base which ties up
H+:
l
the carbonic acid dissociates into H+ and bicarbonate ions
The weak bicarbonate base replaces the strong base
l


Copyright © John Wiley & Sons, Inc. All rights reserved.
Chemical Buffer Systems

Phosphate buffer system

Important intracellular buffer, but also acts to buffer
acids in the urine

Works the same way as the carbonic acid- bicarbonate
system

Protein buffer system

Buffer in cells & in plasma

Hemoglobin is an important buffer which binds H+ released
from H2CO3 formed during transport of CO2

Albumin is main protein buffer in plasma
Copyright © John Wiley & Sons, Inc. All rights reserved.
Respiratory Regulation of pH: Exhalation of
Carbon Dioxide

Respiratory system acts by changing the rate and depth of breathing,
CO2 is exhaled or retained, and blood pH is corrected

CO2 formed by cell respiration enters RBCs & is converted to
HCO3¯ for transport in plasma
CO2 + H2O  H2CO3  H+ + HCO3¯

Normally released H+ are buffered by Hb

An increase in CO2 , increases H+ concentration, thus lowers the pH
(makes body fluids more acidic)

An decrease in CO2 , decreases H+ concentration, thus raises the pH
(makes body fluids more alkaline)
Copyright © John Wiley & Sons, Inc. All rights reserved.
Respiratory Regulation of pH: Exhalation of
Carbon Dioxide

Changes in rate & depth of breathing can alter the pH
within minutes:

An increase in the rate and depth of breathing causes
more carbon dioxide to be exhaled, lowering pCO2 levels
in blood; thereby increasing pH.

A decrease in respiration rate and depth means that less
carbon dioxide is exhaled, increasing CO2 levels in blood
causing the blood pH to fall.
Copyright © John Wiley & Sons, Inc. All rights reserved.

pH & rate & depth of
breathing interact by a
negative feedback loop:

Low pH detected by
chemoreceptors in medulla,
carotid & aortic bodies

Increases rate & depth of
breathing; more CO2
exhaled: blood pH goes back
up to normal
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Need for Renal Mechanisms

Chemical buffers prevent changes in pH, but
they cannot eliminate acids & bases from the
body

The body produces nonvolatile acids such as
lactic acids, uric acid, ketone bodies etc, unlike
volatile acid H2CO3, they cannot be removed by
lungs- have to be removed by the kidneys

Therefore although slow acting the ultimate acidbase regulatory organs are the kidneys
Copyright © John Wiley & Sons, Inc. All rights reserved.
Acid-Base Balance
Kidneys control acid base balance by excreting:
l
Acidic urine– reducing the amount of acid in ECF
l
Alkaline urine- removing base in urine

 The kidneys regulates acid base balance mainly by
reabsorption of HCO3¯ & secretion of H+:
l
The kidneys prevent the loss of filtered HCO3¯
conserving this important buffer
l
They secrete H+ to get rid of excess acid
 Both the PCT & collecting ducts secrete H+ and reabsorb
HCO3¯
Copyright © John Wiley & Sons, Inc. All rights reserved.
Kidney excretion of H+ -PCT

Within PCT cells H+ and
bicarbonate ion produced

Na+/H+ antiporters used to
secrete H+ while bicarbonate
reabsorbed into peritubular capillaries

H+ secreted into the tubular fluid,
combines with filtered bicarbonate
to form CO2 & water

H+ secreted but not actually
excreted in urine
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Kidney excretion of H+ in Collecting ducts

Within intercalated cells H+ and
bicarbonate ion are produced

The intercalated cells have proton pumps
(H+ ATPases) that secrete H+ into the
tubular fluid, while HCO3– reabsorbed

H+ secreted is actually excreted in urine;
can create very acidic urine

If pH of blood too alkaline other
intercalated cells can secrete HCO3– and
reabsorb H+
Copyright © John Wiley & Sons, Inc. All rights reserved.
Respiratory Acidosis and Alkalosis

Respiratory system itself the cause of pH imbalance; caused by
changed levels of pCO2



Respiratory acidosis:
Arterial blood pCO2 above 45mmHg
Occurs when a person breathes shallowly, or gas exchange is
hampered by diseases such as pneumonia, emphysema,
pulmonary edema
CO2 accumulates in blood-rise in pCO2 causes fall in pH






Respiratory alkalosis:
Arterial blood pCO2 below 35mmHg
CO2 is eliminated faster than it is produced- pH becomes
alkaline
Common result of hyperventilation- stress, panic, stroke
Renal compensation can help keep pH within normal range
by controlling H+ secretion& HCO3 reabsorption
Copyright © John Wiley & Sons, Inc. All rights reserved.
Metabolic Acidosis and Alkalosis




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

Metabolic pH imbalances – from disturbances in plasma
HCO3¯
Include pH imbalances except those caused by abnormal
blood carbon dioxide levels
Metabolic Acidosis
Low bicarbonate levels , low pH
Causesexcessive loss of bicarbonate ions in diarrhea
accumulation of lactic acid, keto acids in diabetic crisis
kidney failure- failing kidney unable to excrete H+
Respiratory compensation through hyperventilation may
bring pH into normal range
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Metabolic Acidosis and Alkalosis

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)

Gastric suctioning

Respiratory compensation through hypoventilation may bring
pH into normal range
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