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Chapter Notes for Lecture: E.N. Marieb, HUMAN ANATOMY & PHYSIOLOGY,5TH Edition, , Benjamine Cummings Publisher, 2001 Prepare from : V.A. Austin’s PowerPpoint Presentation (ISBN: 0-8053-5469-7), CD ROM: Pearson Education, Inc. , 2003.


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


•      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 cell’s 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 body’s 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