Fluid, Electrolyte, and Acid-Base Balance

I Patel

2020
• Discuss the importance of:
- fluid balance
- electrolyte balance; and
- acid-base balance for homeostasis

2
 FLUID BALANCE
• Is a daily balance between:
• Amount of water gained
• Amount of water lost to environment
• Involves regulating content and distribution of body water in ECF and ICF
• The Digestive System
• Is the primary source of water gains
•Plus a small amount from metabolic activity
• The Urinary System
• Is the primary route of water loss

3
FLUID BALANCE
 ELECTROLYTE BALANCE
• Electrolytes are ions released through dissociation of inorganic compounds
• Can conduct electrical current in solution
• Electrolyte balance
• When the gains and losses of all electrolytes are equal
• Primarily involves balancing rates of absorption across digestive tract with
rates of loss at kidneys and sweat glands

5
ELECTROLYTE BALANCE

6
 ACID–BASE BALANCE

• Precisely balances production and loss of hydrogen ions (pH)

• The body generates acids during normal metabolism
• Tends to reduce pH

7
• Distinguish between ICF and ECF fluid compartments
• Explain the basic concepts involved in the regulation of
fluids and electrolytes
• Identify the hormones that play a role in fluid and
electrolyte regulation

8
 The ICF and the ECF are two distinct fluid compartments

• ICF
• The cytosol of cells
• Makes up about two-thirds of the total body water
• ECF
• Major components: interstitial fluid & plasma
• Minor components: other extracellular fluids i.e. lymph, CSF, synovial fluid,
humors of the eye, peri- & endolymph

9 9
 Extracellular Fluid Compartments

• Major Subdivisions of ECF

• Interstitial fluid of peripheral tissues
• Plasma of circulating blood
• Minor Subdivisions of ECF
• Lymph, perilymph, and endolymph
• Cerebrospinal fluid (CSF)
• Synovial fluid
• Serous fluids (pleural, pericardial, and peritoneal)
• Aqueous humor

10
 The Composition of the Human Body
SOLID COMPONENTS
(31.5 kg; 69.3 lbs)

Kg

Proteins Lipids Minerals Carbohydrates Miscellaneous

The body composition (by weight, averaged for both
sexes) and major body fluid compartments of a 70-kg
individual.
11
 The Composition of the Human Body

WATER 60% WATER 50%

ICF ICF ECF

ECF Intracellular Interstitial
Intracellular Interstitial
fluid 33% fluid 21.5% fluid 27% fluid 18%
Plasma 4.5% Other
Plasma 4.5% body
Solids 50% fluids
Solids 40% Other
(organic and inorganic materials) (1%)
(organic and inorganic materials) body
fluids
(1%)

SOLIDS 40%
SOLIDS 50%
Adult males
Adult females

12
 The Composition of the Human Body
WATER (38.5 kg; 84.7 lbs)

Other

Plasma

Liters

Interstitial
fluid

Intracellular fluid Extracellular fluid

The body composition (by weight, averaged
for both sexes) and major body fluid
compartments of a 70-kg individual.

13
 The ECF and the ICF

• ECF Solute Content

• Types and amounts vary regionally
• Electrolytes
• Proteins
• Nutrients
• Waste products

14
 The ECF and the ICF

• Are called fluid compartments because they behave as distinct entities

• Are separated by plasma membranes and active transport
• Cations and Anions
• In ECF
• Sodium, chloride, and bicarbonate
• In ICF
• Potassium, magnesium, and phosphate ions
• Negatively charged proteins

15
 Cations and Anions in Body Fluids
CATIONS ANIONS
ECF ICF ECF ICF

Na HCO3
Cl
Milliequivalents per liter (mEq/L)

HCO3
HCO3
HPO42
K

Na Cl
Na
Cl SO42

HPO42
Proteins
Org. acid
Mg2 HPO42
K  Proteins SO42
Ca2 K

Plasma Interstitial Intracellular Plasma Interstitial Intracellular 16

fluid fluid fluid fluid
 Basic Concepts in the Regulation of Fluids and Electrolytes

1. All homeostatic mechanisms that monitor and adjust body fluid

composition respond to changes in the ECF, not in the ICF
2. No receptors directly monitor fluid or electrolyte balance
3. Cells cannot move water molecules by active transport
4. The body’s water or electrolyte content will rise if dietary gains
exceed environmental losses, and will fall if losses exceed
gains

17
 An Overview

• Primary Regulatory Hormones Affecting fluid and electrolyte

balance
1. Antidiuretic hormone (ADH)
2. Aldosterone
3. Natriuretic peptides

18
 Antidiuretic Hormone (ADH)

• ADH Production
• Osmoreceptors in hypothalamus
• Monitor osmotic concentration of ECF
• Change in osmotic concentration
• Alters osmoreceptor activity
• Osmoreceptor neurons secrete ADH

• Stimulates water conservation at kidneys

• Reducing urinary water loss
• Concentrating urine
• Stimulates thirst center
• Promoting fluid intake

19
Antidiuretic Hormone (ADH)

20
 Aldosterone

• Is secreted by adrenal cortex in response to:

• Rising K+ or falling Na+ levels in blood
• Activation of renin–angiotensin system
• Determines rate of Na+ absorption and K+ loss along DCT and collecting system
• “Water Follows Salt”
• High aldosterone plasma concentration
• Causes kidneys to conserve salt
• Conservation of Na+ by aldosterone
• Also stimulates water retention

21
Aldosterone

22
 Natriuretic Peptides

• ANP is released by cardiac muscle cells

• In response to abnormal stretching of heart walls (BP/volume)
• Reduces thirst
• Blocks release of ADH and aldosterone
• Causes diuresis
• Lowers blood pressure and plasma volume

24
Natriuretic Peptides

25
• Describe the movement of fluid:
• within the ECF;
• between ECF and ICF; and
• between ECF and the environment

27
 Movement of Water and Electrolytes

• When the body loses water:

• Plasma volume decreases
• Electrolyte concentrations rise
• When the body loses electrolytes:
• Water is lost by osmosis
• Regulatory mechanisms are different

28
• Water circulates freely in ECF compartment
• At capillary beds, hydrostatic pressure forces water out of plasma and into interstitial
spaces
• Water is reabsorbed along distal portion of capillary bed when it enters lymphatic vessels
• ECF and ICF are normally in osmotic equilibrium
• No large-scale circulation between compartments

29
 Fluid Movement within the ECF

• Net hydrostatic pressure

• Pushes water out of plasma
• Into interstitial fluid
• Net colloid osmotic pressure
• Draws water out of interstitial fluid
• Into plasma

30
 Fluid Movement within the ECF

• ECF fluid volume is redistributed

• From lymphatic system to venous system (plasma)
• Interaction between opposing forces
• Results in continuous filtration of fluid
• ECF volume
• Is 80% in interstitial fluid and minor fluid compartment
• Is 20% in plasma

32
• Edema
• The movement of abnormal amounts of water from plasma into interstitial fluid
• Lymphedema
• Edema caused by blockage of lymphatic drainage

33
Fluid Gains and Losses

Water absorbed across

digestive epithelium
(2200mL)
Water vapor lost
in respiration and
evaporation from
moist surfaces
(1150 mL)

Metabolic Water lost in

ICF water ECF feces (150 mL)
(300 mL)
Water secreted
by sweat glands
(variable)

Plasma membranes Water lost in urine

(1200mL)

34
Water Balance

35
Fluid Shifts between the ICF and ECF

36
Allocation of Water Losses

37
 Fluid Shifts

• Are rapid water movements between ECF and ICF

• In response to an osmotic gradient

• Isotonic
• Hypertonic
• Hypotonic

• ICF volume is much greater than ECF volume

• ICF acts as water reserve
• Prevents large osmotic changes in EC

38
• If ECF osmotic concentration increases:
• Fluid becomes hypertonic to ICF
• Water moves from cells to ECF

39
• If ECF osmotic concentration decreases:
• Fluid becomes hypotonic to ICF
• Water moves from ECF to cells

40
 Allocation of Water Losses

• Dehydration (Water Depletion)

• Develops when water loss is greater than gain
• If water is lost, but electrolytes retained:
• ECF osmotic concentration rises
• Water moves from ICF to ECF
• Net change in ECF is small
• May result in thirst, dryness, wrinkling, shock

41
 Severe Water Loss
• Causes:
• Excessive perspiration
• Inadequate water consumption
• Repeated vomiting
• Diarrhea
• Homeostatic responses
• Physiologic mechanisms (ADH and renin secretion)
• Behavioral changes (increasing fluid intake)
• Clinical therapy

42
Distribution of Water Gains

43
 Distribution of Water Gains
• If water is gained, but electrolytes are not:
• ECF volume increases
• ECF becomes hypotonic to ICF
• Fluid shifts from ECF to ICF
• Decreased ADH
• May result in overhydration (water excess)
• Occurs when excess water shifts into ICF
• Distorting cells
• Changing solute concentrations around enzymes
• Disrupting normal cell functions

44
 Causes of Overhydration

• Ingestion of large volume of fresh water

• Injection of hypotonic solution into bloodstream
• Endocrine disorders
• Excessive ADH production
• Inability to eliminate excess water in urine
• Chronic renal failure
• Heart failure
• Cirrhosis
• Signs of Overhydration
• Abnormally low Na+ concentrations (hyponatremia)
• Effects on CNS function (water intoxication)

45
• Describe the mechanisms by which, Sodium, Potassium, Calcium & Chloride
Concentrations are regulated to maintain electrolyte balance

46
 Electrolyte Balance
• Requires rates of gain and loss of each electrolyte in the body to be equal
• Electrolyte concentration directly affects water balance
• Concentrations of individual electrolytes affect cell functions

47
 SODIUM

• Is the dominant cation in ECF

• Sodium salts provide 90% of ECF osmotic concentration
• Sodium chloride (NaCl)
• Sodium bicarbonate (NaHCO3)
• Normal Sodium Concentrations
• In ECF
• About 140 mEq/L
• In ICF
• Is 10 mEq/L or less

48
SODIUM BALANCE

49
 Sodium Balance

• Total amount of sodium in ECF represents a balance between two factors

1. Sodium ion uptake across digestive epithelium
2. Sodium ion excretion in urine and perspiration

50
The Homeostatic Regulation of Normal Sodium Ion Concentrations in Body Fluids
ADH Secretion Increases Recall of Fluids
The secretion of ADH Because the ECF
restricts water loss and osmolarity increases,
stimulates thirst, promoting water shifts out of
additional water the ICF, increasing
consumption. ECF volume and
lowering Na
concentrations.
Osmoreceptors
in hypothalamus
stimulated

HOMEOSTASIS
HOMEOSTASIS RESTORED
DISTURBED
Decreased Na
Increased Na levels in ECF
levels in ECF

HOMEOSTASIS
Start
Normal Na
concentration
in ECF
The Homeostatic Regulation of Normal Sodium Ion Concentrations in Body Fluids

HOMEOSTASIS
Start
Normal Na
concentration
in ECF
HOMEOSTASIS HOMEOSTASIS
DISTURBED RESTORED
Decreased Na Increased Na
levels in ECF levels in ECF

Osmoreceptors Water loss reduces

in hypothalamus ECF volume,
inhibited concentrates ions
ADH Secretion Decreases
As soon as the osmotic
concentration of the ECF
drops by 2 percent or more,
ADH secretion decreases, so
thirst is suppressed and
water losses at the kidneys
increase.
 Homeostatic Mechanisms

• A rise in blood volume elevates blood pressure

• A drop in blood volume lowers blood pressure
• Monitor ECF volume indirectly by monitoring blood pressure
• Baroreceptors at carotid sinus, aortic sinus, and right atrium

• Hyponatremia
• Body water content rises (overhydration)
• ECF Na+ concentration <136 mEq/L
• Hypernatremia
• Body water content declines (dehydration)
• ECF Na+ concentration >145 mEq/L

53
Homeostatic Mechanisms

54
• ECF Volume
• If ECF volume is inadequate:
• Blood volume and blood pressure decline
• Renin–angiotensin system is activated
• Water and Na+ losses are reduced
• ECF volume increases
• Plasma Volume
• If plasma volume is too large:
• Venous return increases
• Stimulating release of natriuretic peptides (ANP)
• Reducing thirst
• Blocking secretion of ADH and aldosterone
• Salt and water loss at kidneys increases
• ECF volume declines
 The Integration of Fluid Volume Regulation and Sodium Ion Concentrations in Body
Fluids
Responses to Natriuretic Peptides Combined
Effects
Increased Na loss in urine
Reduced
Rising blood Increased water loss in urine blood
pressure and Natriuretic peptides volume
released by cardiac Reduced thirst
volume
muscle cells Reduced
Inhibition of ADH, aldosterone, blood
epinephrine, and norepinephrine pressure
release
Increased blood
volume and
atrial distension

HOMEOSTASIS
HOMEOSTASIS
RESTORED
DISTURBED
Rising ECF volume by fluid Falling ECF
gain or fluid and Na gain volume
HOMEOSTASIS
Start
Normal ECF
volume

56
 The Integration of Fluid Volume Regulation and Sodium Ion Concentrations in Body
Fluids

HOMEOSTASIS
Start
Normal ECF
HOMEOSTASIS volume HOMEOSTASIS
DISTURBED RESTORED
Falling ECF volume by fluid Rising ECF
loss or fluid and Na loss volume

Decreased blood
volume and
Endocrine Responses Combined Effects
blood pressure Increased renin secretion Increased urinary Na
and angiotensin II retention
activation Decreased urinary water
Increased aldosterone loss
Falling blood release Increased thirst
pressure and
Increased ADH release Increased water intake
volume

57
 POTASSIUM BALANCE

• 98% of potassium in the human body is in ICF

• Cells expend energy to recover potassium ions diffused from cytoplasm into ECF
• Processes of Potassium Balance
1. Rate of gain across digestive epithelium
2. Rate of loss into urine
• Normal potassium concentrations
• In ICF
• About 160 mEq/L
• In ECF
• 3.5–5.5 mEq/L

58
POTASSIUM BALANCE

59
• Potassium Loss in Urine
• Is regulated by activities of ion pumps
• Along distal portions of nephron and collecting system
• Na+ from tubular fluid is exchanged for K+ in peritubular fluid
• Factors in Tubular Secretion of K+
1. Changes in K+ concentration of ECF
2. Changes in pH
3. Aldosterone levels

60
1. Changes in Concentration of K + in ECF
• Higher ECF concentration increases rate of secretion

2. Changes in pH
• Low ECF pH lowers peritubular fluid pH
• H+ rather than K+ is exchanged for Na+ in tubular fluid
• Rate of potassium secretion declines

61
3. Aldosterone Levels
• Affect K+ loss in urine
• Ion pumps reabsorb Na+ from filtrate in exchange for K+ from peritubular fluid
• High K+ plasma concentrations stimulate aldosterone

62
 Major Factors Involved in Disturbances of Potassium Balance

When the plasma concentration of potassium falls below 2 High K concentrations in the ECF produce an equally
mEq/L, extensive muscular weakness develops, followed by Normal potassium dangerous condition known as hyperkalemia. Severe
eventual paralysis. This condition, called hypokalemia (kalium, levels in serum: cardiac arrhythmias appear when the K concentration
potassium), is potentially lethal due to its effects on the heart. (3.5–5.0 mEq/L) exceeds 8 mEq/L.

Factors Promoting Hypokalemia Factors Promoting Hyperkalemia

Several diuretics, The endocrine disorder Chronically low Kidney failure due to Several drugs promote
including Lasix, called aldosteronism, body fluid pH damage or disease diuresis by blocking Na
can produce characterized by excessive promotes will prevent normal reabsorption at the kidneys.
hypokalemia by aldosterone secretion, hyperkalemia by K secretion and When sodium reabsorption
increasing the results in hypokalemia by interfering with K thereby produce slows down, so does
volume of urine overstimulating sodium excretion at the hyperkalemia. potassium secretion, and
produced. retention and potassium loss. kidneys. hyperkalemia can result.

63
Electrolyte Balance for Average Adult

64
 CALCIUM BALANCE

• Calcium is most abundant mineral in the body

• A typical individual has 1–2 kg of this element
• 99% of which is deposited in skeleton
• Functions of Calcium Ion (Ca2+)
• Muscular and neural activities
• Blood clotting
• Cofactors for enzymatic reactions
• Second messengers

65
CALCIUM BALANCE

66
 Hormones and Calcium Homeostasis

• Parathyroid hormone (PTH) and calcitriol

• Raise calcium concentrations in ECF
• Calcitonin
• Opposes PTH and calcitriol

67
• Calcium Absorption
• At digestive tract and reabsorption along DCT
• Is stimulated by PTH and calcitriol

• Calcium Ion Loss

• In bile, urine, or feces
• Is very small (0.8–1.2 g/day)
• Represents about 0.03% of calcium reserve in skeleton

68
 Disorders of Calcium Imbalance
• Hypercalcemia
• Exists if Ca2+ concentration in ECF is >5.3 mEq/L
• Is usually caused by hyperparathyroidism
• Resulting from oversecretion of PTH
• Other causes
• Malignant cancers (breast, lung, kidney, bone marrow)
• Excessive calcium or vitamin D supplementation
• Hypocalcemia
• Exists if Ca2+ concentration in ECF is <4.3 mEq/L
• Is much less common than hypercalcemia
• Is usually caused by chronic renal failure
• May be caused by hypoparathyroidism,
• Resulting from under-secretion of PTH, Vitamin D deficiency
69
70
 Study questions

• Describe three factors that affect tubular secretion of potassium.

• What is the role of aldosterone in sodium and fluid balance?
• What is the effect of prolonged sweating on electrolyte levels?
• Describe the effect of drinking a hypertonic solution on fluid and electrolyte balance
• What is the physiological relevance of regulating calcium ions?

71
• Introduction to pH regulation
• Explain the importance of pH control

72
Acid–Base Balance

73
 Acid–Base Balance

• pH of body fluids is altered by addition or deletion of acids or bases

• Acids and bases may be strong or weak
• Strong acids and strong bases
• Dissociate completely in solution
• Weak acids or weak bases
• Do not dissociate completely in solution
• Some molecules remain intact
• Liberate fewer hydrogen ions
• Have less effect on pH of solution

74
A Review of Important Terms Relating to Acid–Base Balance
 The Importance of pH Control

• pH of body fluids depends on dissolved:

• Acids
• Bases
• Salts
• pH of ECF
• Is narrowly limited, usually 7.35–7.45

76
• Acidosis
• Physiological state resulting from abnormally low plasma pH
• Acidemia plasma pH < 7.35
• Alkalosis
• Physiological state resulting from abnormally high plasma pH
• Alkalemia plasma pH > 7.45

77
• Acidosis and Alkalosis
• Affect all body systems
• Particularly nervous and cardiovascular systems
• Both are dangerous
• But acidosis is more common
• Because normal cellular activities generate acids
• Disrupt membrane stability
• Change protein structure
• Alter enzyme activity
• Result in coma, cardiac failure, and circulatory collapse

78
• Distinguish between different types of acids in the body

79
 Types of Acids in the Body

1. Fixed acids
2. Organic acids
3. Volatile acids

80
 FIXED ACIDS

• Are acids that do not leave solution

• Once produced they remain in body fluids until eliminated by kidneys
• Sulfuric acid and phosphoric acid
• Are most important fixed acids in the body
• Are generated during catabolism of:
• Amino acids
• Phospholipids
• Nucleic acids

81
 ORGANIC ACIDS

• Produced by/take part in cellular metabolism

• Are metabolized rapidly
• Do not accumulate
• Lactic Acid
• Ketone bodies

82
 VOLATILE ACIDS
• A volatile acid that can leave solution and enter the atmosphere at the lungs (e.g. carbonic
acid generated from CO2)
• CO2 reacts with water to form carbonic acid
• At the lungs, carbonic acid breaks down into carbon dioxide and water

H2O + CO2  H2CO3

Carbon dioxide diffuses into alveoli

83
 Categories of Acids

 C3H4O3
 H2SO4  C3H6O3
 H3PO4  C4H6O3

H20 + CO2  H2CO3

84
Carbonic Acid

H20 + CO2  H2CO3

85
 Carbonic Acid

• H2O + CO2  H2CO3

• Is a weak acid
• In ECF at normal pH equilibrium state exists

• Carbonic acid is the most important factor affecting pH of ECF

• Inverse relationship between pH and concentration of CO2

86
 Carbonic Anhydrase

• Enzyme that catalyzes dissociation of carbonic acid

• Found in:
• Cytoplasm of red blood cells
• Liver and kidney cells
• Parietal cells of stomach
• Other cells

87
 CO2 and pH

• When CO2 levels rise:

• H+ and bicarbonate ions are released
• pH goes down
• When CO2 levels decrease:
• CO2 diffuses into atmosphere at the alveoli
• H+ and bicarbonate ions in alveolar capillaries drop
• Blood pH rises

88
Relationship between PCO2 & Plasma pH

89
• Distinguish between the functioning and roles of the three
major buffer systems in the body:
• protein buffer system
• carbonic acid-bicarbonate buffer system and
• phosphate buffer system

92
 Mechanisms of pH Control

• To maintain acid–base balance:

• The body balances gains and losses of hydrogen ions
• And gains and losses of bicarbonate ions
• Hydrogen Ions (H+)
• Are gained:
• At digestive tract & through cellular metabolic activities
• Are eliminated:
• At kidneys in urine & at lungs
• Must be neutralized to avoid tissue damage
• Acids produced in normal metabolic activity are temporarily neutralized by buffers in body
fluids

93
Mechanisms of pH Control

94
 Buffers

• Are dissolved compounds that stabilize pH by providing or removing H+

• Weak acids
• Can donate H+
• Weak bases
• Can absorb H+

95
 Buffers

HY H+ + Y-

96
 Buffer System
• Consists of a combination of:
• A weak acid
• And the anion released by its dissociation
• The anion functions as a weak base

HY H+ + Y-
• In solution, molecules of weak acid exist in equilibrium with its dissociation products
• Act as a first line, TEMPORARY solution

97
 Three Major Buffer Systems

1. Protein buffer systems

• Help regulate pH in ECF and ICF
• Interact extensively with other buffer systems
2. Carbonic acid–bicarbonate buffer system
• Most important in ECF
3. Phosphate buffer system
• Buffers pH of ICF and urine

98
 Buffer Systems in Body Fluids

Buffer Systems
occur in

Intracellular fluid (ICF) Extracellular fluid (ECF)

Phosphate Buffer Protein Buffer Systems Carbonic Acid–

System Bicarbonate Buffer
Protein buffer systems contribute to the regulation System
The phosphate of pH in the ECF and ICF. These buffer systems interact
buffer system extensively with the other two buffer systems. The carbonic acid–
has an important bicarbonate buffer
role in buffering system is most
the pH of the ICF important in the ECF.
and of urine. Amino acid buffers
Hemoglobin buffer Plasma protein
system (RBCs only) (All proteins) buffers

99
 PROTEIN BUFFER SYSTEMS
• Depend on amino acids
• Respond to pH changes by accepting or releasing H+

100
PROTEIN BUFFER SYSTEMS

101
 PROTEIN BUFFER SYSTEMS
• If pH rises:
• Carboxyl group (-COOH) of amino acid dissociates
• Acting as weak acid, releasing a hydrogen ion
• Carboxyl group becomes carboxylate ion (-COO-)
• At normal pH (7.35–7.45)
• Carboxyl groups of most amino acids have already given up their H+
• If pH drops:
• Carboxylate ion and amino group (-NH2) act as weak bases
• Accept H+ & Form carboxyl group and amino ion (-NH3+)

102
The Role of Amino Acids in Protein Buffer Systems

103
 The Hemoglobin Buffer System

• CO2 diffuses across RBC membrane

• No transport mechanism required
• As carbonic acid dissociates:
• Bicarbonate ions diffuse into plasma
• In exchange for chloride ions (chloride shift)
• Hydrogen ions are buffered by hemoglobin molecules
• Is the only intracellular buffer system with an immediate effect on ECF pH
• Helps prevent major changes in pH when plasma PCO is rising or falling
2

104
A Summary of the Primary Gas Transport Mechanisms
A Summary of the Primary Gas Transport Mechanisms
 CARBONIC ACID–BICARBONATE BUFFER SYSTEM

• H2O + CO2  H2CO3  H+ + HCO3–

• Carbon dioxide
• Most body cells constantly generate carbon dioxide
• Most carbon dioxide is converted to carbonic acid, which dissociates into H+ and a
bicarbonate ion
• Is formed by carbonic acid and its dissociation products
• Prevents changes in pH caused by organic acids and fixed acids in ECF by converting them
to volatile CO2

107
CARBONIC ACID–BICARBONATE BUFFER SYSTEM

108
 Limitations of The Carbonic Acid–Bicarbonate Buffer System

1. Cannot protect ECF from changes in pH that result from elevated or depressed levels of
CO2 (It’s own weak acid)
2. Functions only when respiratory system and respiratory control centers are working
normally
3. Ability to buffer acids is limited by availability of bicarbonate ions
• Bicarbonate ion shortage is rare
• Due to large reserve of sodium bicarbonate (NaHCO3) called the bicarbonate reserve
• Bicarbonate can be generated by the kidneys

109
The Carbonic Acid-Bicarbonate Buffer System

110
 THE PHOSPHATE BUFFER SYSTEM

• Consists of anion H2PO4– (a weak acid)

• Works like the carbonic acid–bicarbonate buffer system
• Is important in buffering pH of ICF

H2PO4– H+ + HPO42–

• The phosphate buffer system also stabilizes urine pH

111
 THE PHOSPHATE BUFFER SYSTEM

H2PO4– H+ + HPO42–

112
 Limitations of Buffer Systems

• Provide only temporary solution to acid–base imbalance

• Do not eliminate H+ ions
• Supply of buffer molecules is limited

113
• Describe the respiratory and renal compensatory mechanisms
involved in the maintenance of acid-base balance

114
 Maintenance of Acid–Base Balance

• Requires balancing H+ gains and losses

• Coordinates actions of buffer systems with:
• Respiratory mechanisms
• Renal mechanisms
• Respiratory and Renal Mechanisms
• Support buffer systems by:
1. Secreting or absorbing H+
2. Controlling excretion of acids and bases
3. Generating additional buffers

115
 RESPIRATORY COMPENSATION

• Is a change in respiratory rate that helps stabilize pH of ECF

• Occurs whenever body pH moves outside normal limits
• Directly affects carbonic acid–bicarbonate buffer system
• Increasing or decreasing the rate of respiration alters pH by lowering or raising the PCO2
• When PCO rises:
2
• pH falls
• Addition of CO2 drives buffer system to the right
• When PCO falls:
2
• pH rises
• Removal of CO2 drives buffer system to the left

116
Relationship between PCO2 & Plasma pH

117
 The Chemoreceptor Response to Changes in PCO2

Stimulation Stimulation of
of arterial respiratory muscles
chemoreceptors

Increased Increased PCO2 , Stimulation of CSF

arterial PCO2 decreased pH chemoreceptors at
in CSF medulla oblongata

HOMEOSTASIS Increased respiratory

DISTURBED rate with increased
elimination of CO2 at
Increased alveoli
arterial PCO2
(hypercapnia)

HOMEOSTASIS
HOMEOSTASIS
RESTORED
Start
Normal Normal
arterial PCO2 arterial PCO2

118
 The Chemoreceptor Response to Changes in PCO2

HOMEOSTASIS
HOMEOSTASIS
RESTORED
Start
Normal Normal
arterial PCO2 arterial PCO2

HOMEOSTASIS
DISTURBED Decreased respiratory
rate with decreased
Decreased elimination of CO2 at
arterial PCO2 alveoli
(hypocapnia)

Decreased Decreased PCO2 ,

arterial PCO Reduced stimulation
2 increased pH
of CSF chemoreceptors
in CSF

Inhibition of arterial Inhibition of

chemoreceptors respiratory muscles

119
Renal Response to Acidosis

120
Renal Response to Alkalosis

121
 RENAL COMPENSATION

• Kidneys help regulate pH through renal compensation

• Is a change in rates of H+ and HCO3– secretion or reabsorption by kidneys in response to
changes in plasma pH
• The body normally generates enough organic and fixed acids each day to add 100 mEq of H+
to ECF
• Kidneys assist lungs by eliminating any CO2 that:
• Enters renal tubules during filtration
• Diffuses into tubular fluid en route to renal pelvis

122
 Renal Responses to Acidosis

• Acidosis develops due to increase in H+ levels

1. Secretion of H+
2. Activity of buffers in tubular fluid
3. Removal of CO2
4. Reabsorption of NaHCO3–

123
 Interactions among the Carbonic Acid–Bicarbonate Buffer System and
Compensatory Mechanisms in the Regulation of Plasma pH

The response to acidosis caused by the addition of H

Addition
Start
of H

CARBONIC ACID-BICARBONATE BUFFER SYSTEM BICARBONATE RESERVE

CO2 CO2  H2O H2CO3 H  HCO3 HCO3  Na NaHCO3

(carbonic acid) (bicarbonate ion) (sodium bicarbonate)
Lungs
Generation
Other of HCO3
Respiratory Response KIDNEYS
to Acidosis buffer
systems Renal Response to Acidosis
Increased respiratory absorb H
rate lowers PCO ,
2 Kidney tubules respond by (1) secreting H
effectively converting ions, (2) removing CO2, and (3) reabsorbing
carbonic acid Secretion HCO3 to help replenish the bicarbonate
molecules to water. of H reserve.

124
 Interactions among the Carbonic Acid–Bicarbonate Buffer System and
Compensatory Mechanisms in the Regulation of Plasma pH

The response to alkalosis caused by the removal of H

Removal
Start
of H

CARBONIC ACID-BICARBONATE BUFFER SYSTEM BICARBONATE RESERVE

Lungs CO2  H2O H2CO3 H  HCO3 HCO3  Na NaHCO3

(carbonic acid) (bicarbonate ion) (sodium bicarbonate)

Respiratory Response Other Generation

to Alkalosis buffer of H KIDNEYS

systems
Decreased respiratory release H Renal Response to Alkalosis
rate elevates PCO ,
2
effectively converting Kidney tubules respond by
CO2 molecules to conserving H ions and
Secretion secreting HCO3.
carbonic acid.
of HCO3

125
 The three major buffering systems in tubular fluid,
which are essential to the secretion of hydrogen ions
 Renal Responses to Alkalosis

1. Rate of H+ secretion at kidneys declines

2. Tubule cells do not reclaim bicarbonates in tubular fluid
3. Collecting system transports HCO3– into tubular fluid while releasing strong acid (HCl)
into peritubular fluid
4. HCO3– concentration decreases promoting the dissociation of H2CO3 to release H+ - thus
returning the pH back to normal

127
• Explain how the body responds when the pH of body fluids
varies outside normal limits:
• respiratory acidosis
• respiratory alkalosis
• metabolic acidosis
• metabolic alkalosis

128
 Acid–Base Balance Disturbances

• Disorders
• Circulating buffers
• Respiratory performance
• Renal function
• Cardiovascular conditions
• Heart failure
• Hypotension
• Conditions affecting the CNS
• Neural damage or disease that affects respiratory and cardiovascular reflexes

129
• Respiratory Acid–Base Disorders
• Result from imbalance between:
• CO2 generation in peripheral tissues
• CO2 excretion at lungs
• Cause abnormal CO2 levels in ECF

• Metabolic Acid–Base Disorders

• Result from:
• Generation of organic or fixed acids
• Conditions affecting HCO3- concentration in ECF

130
 Respiratory Acidosis

• Develops when the respiratory system cannot eliminate all CO2 generated by peripheral
tissues
• Primary sign
• Low plasma pH due to hypercapnia
• Primary cause
• Hypoventilation
• Acute RA – Life Threatening  Remember your ABC’s
• Chronic RA – respiratory response has not failed completely

131
 Respiratory Acid–Base Regulation

Responses to Acidosis

Respiratory compensation:
Stimulation of arterial and CSF chemo-
Increased receptors results in increased
PCO respiratory rate.
2
Renal compensation:
Combined Effects
H ions are secreted and HCO3
Respiratory Acidosis ions are generated. Decreased PCO
2
Elevated PCO results Buffer systems other than the carbonic 
Decreased H and
2
in a fall in plasma pH acid–bicarbonate system accept H ions. increased HCO3

HOMEOSTASIS HOMEOSTASIS
DISTURBED RESTORED
HOMEOSTASIS
Hypoventilation Plasma pH
causing increased PCO Normal returns to normal
2
acid–base
balance
Respiratory acidosis

132
 Respiratory Alkalosis

• Relatively rare condition that develops when respiratory system lowers PCO2
• Primary sign
• High plasma pH due to hypocapnia
• Primary cause
• Hyperventilation

133
 Respiratory Acid–Base Regulation

HOMEOSTASIS
HOMEOSTASIS HOMEOSTASIS
DISTURBED Normal RESTORED
acid–base
Hyperventilation balance Plasma pH
causing decreased PCO returns to normal
2

Respiratory Alkalosis Combined Effects

Responses to Alkalosis
Lower PCO results Increased PCO
2 Respiratory compensation: 2
in a rise in plasma pH
Inhibition of arterial and CSF Increased H and
chemoreceptors results in a decreased decreased HCO3
respiratory rate.

Renal compensation:
Decreased H ions are generated and HCO3 ions
PCO are secreted.
2
Buffer systems other than the carbonic
acid–bicarbonate system release H
Respiratory alkalosis ions.

134
 Metabolic Acidosis

• Three major causes

1. Production of large numbers of fixed or organic acids
• H+ overloads buffer system
• Lactic acidosis
• Produced by anaerobic cellular respiration
• Ketoacidosis
• Produced by excess ketone bodies
2. Impaired H+ excretion at kidneys
3. Severe bicarbonate loss
• Diarrhea

135
 Responses to Metabolic Acidosis
Responses to Metabolic Acidosis

Respiratory compensation:
Stimulation of arterial and CSF chemo-
Increased receptors results in increased
H ions respiratory rate.

Renal compensation:
H ions are secreted and HCO3 ions
are generated. Combined Effects
Metabolic Acidosis

Elevated H results Buffer systems accept H ions. Decreased H and

in a fall in plasma pH increased HCO3

Decreased PCO
2

HOMEOSTASIS HOMEOSTASIS
DISTURBED HOMEOSTASIS
RESTORED
Normal
Increased H production
acid–base Plasma pH
or decreased H excretion
balance returns to normal

Metabolic acidosis can result from increased

acid production or decreased acid excretion,
leading to a buildup of H in body fluids.

136
 Responses to Metabolic Acidosis
HOMEOSTASIS
HOMEOSTASIS HOMEOSTASIS
DISTURBED Normal RESTORED
acid–base
Bicarbonate loss;
balance Plasma pH
depletion of bicarbonate
returns to normal
reserve

Responses to Metabolic Acidosis Combined Effects

Metabolic Acidosis
Plasma pH falls because Decreased PCO
Respiratory compensation: 2
bicarbonate ions are Stimulation of arterial and CSF chemo- Decreased Hand
unavailable to accept H receptors results in increased increased HCO3
respiratory rate.

Renal compensation:
H ions are secreted and HCO3 ions
Decreased are generated.
HCO3 ions
Buffer systems other than the carbonic
Metabolic acidosis can result
from a loss of bicarbonate acid–bicarbonate system accept H
ions.
ions that makes the carbonic
acid–bicarbonate buffer
system incapable of
preventing a fall in pH.

137
 Metabolic Alkalosis

• Is caused by elevated HCO3– concentrations

• Bicarbonate ions interact with H+ in solution
• Forming H2CO3
• Reduced H+ causes alkalosis
• Common cause is repeated vomitting

138
 Metabolic Alkalosis

HOMEOSTASIS HOMEOSTASIS
DISTURBED HOMEOSTASIS RESTORED

Loss of H; Normal Plasma pH

gain of HCO3 acid–base returns to normal
balance

Metabolic Acidosis Combined Effects

Elevated HCO3 results Increased H and
in a rise In plasma pH Responses to Metabolic Alkalosis decreased HCO3

Respiratory compensation: Increased PCO

2
Stimulation of arterial and CSF
chemoreceptors results in decreased
respiratory rate.
Decreased
H ions, gain Renal compensation:
of HCO3 ions H ions are generated and HCO3
Ions are secreted.

Buffer systems other than the

carbonic acid–bicarbonate system
donate H ions.

139
 Acid–Base Balance Disturbances

• The Detection of Acidosis and Alkalosis

• Includes blood tests for pH, PCO2 and HCO3– levels
’
• Recognition of acidosis or alkalosis
• Classification as respiratory or metabolic

141
 Suspected Acid–Base Disorder

Check pH

Acidosis pH <7.35 (acidemia)

Check PCO
2

Metabolic Acidosis Respiratory Acidosis

PCO normal or decreased PCO increased (>50 mm Hg)
2 2

Primary cause is hypoventilation

Check HCO3–

Acute Chronic Chronic Acute

Metabolic (compensated) (compensated) Respiratory
Acidosis Metabolic Acidosis Respiratory Acidosis Acidosis
PCO normal PCO decreased HCO3– increased HCO3– normal
2
2
(<35 mm Hg) (>28 mEq/L)
Reduction due to Examples
respiratory Examples • respiratory failure
compensation • emphysema • CNS damage
• asthma • pneumothorax

Check anion gap* *The anion gap is defined as:

Na+ concentration – (HCO3– concentration + Cl– concentration)

Normal Increased
Due to loss of HCO3– Due to generation or retention
or to generation or of organic or fixed acids
ingestion of HCl
Examples
Example • lactic acidosis
• diarrhea • ketoacidosis
• chronic renal failure
142
The Anion Gap

143
Suspected Acid–Base Disorder

Check pH

Alkalosis pH >7.45 (alkalemia)

Check PCO
2

Metabolic Respiratory
Alkalosis Alkalosis
PCO increased PCO decreased
2 2
(>45 mm Hg) (<35 mm Hg)
–
(HCO3 will
be elevated)

Examples Primary
• vomiting cause is
• loss of gastric hyperventilation
acid

–
Check HCO3

Acute Chronic
Respiratory (compensated)
Alkalosis Respiratory
Alkalosis
–
Normal or slight Decreased HCO3
decrease (<24 mEq/L)
–
in HCO3
Examples Examples
• fever • anemia
• panic attacks • CNS damage
144
Changes in Blood Chemistry Associated with the
Major Classes of Acid–Base Disorders.

145
The table below shows the results of arterial blood gas analysis for three patients (A, B, and C)
admitted to a Johannesburg hospital.

Blood variable A B C Normal range

pH 7.37 7.38 7.18 7.36-7.44

HCO3- (mmol.ℓ-1) 30 15 16 18-24

PaCO2 (mmHg) 54 26 44 30-37

Na+ (mmol.ℓ-1) 138 140 140 135-147
K+ (mmol.ℓ-1) 5.8 4.5 3.8 3.3-5.3
Cl- (mmol.ℓ-1) 102 105 117 99-113

146
• Explaining your answer and showing any calculations made, decide whether the following
statements are correct or incorrect.
•
• a) Patient A has chronic obstructive pulmonary disease.
• b) Patient B has chronic metabolic acidosis
• c) Patient C has a mixed acid-base disorder.

147
• Describe changes in
total body water
renal capacity
mineral turnover and
compensatory mechanisms
that accompany aging

148
 Changes with age include

• Reduced total body water content

• Impaired ability to perform renal compensation
• Increased water demands
• Reduced ability to concentrate urine
• Reduced sensitivity to ADH/ aldosterone
• Net loss of minerals
• Inability to perform respiratory compensation
• Secondary conditions that affect fluid, electrolyte, acid-base
balance

149 149
 You should now be familiar with:

• What is meant by “fluid balance,” “electrolyte balance,” and “acid-base balance”

• The compositions of intracellular and extracellular fluids
• The hormones that play important roles in regulating fluid and electrolyte balance
• The movement of fluid that takes place within the ECF, between the ECF and the ICF, and
between the ECF and the environment

150 150
 You should now be familiar with:

• How sodium, potassium, calcium and chloride ions are regulated to maintain electrolyte
balance
• The buffering systems that balance the pH of the intracellular and extracellular fluids
• The compensatory mechanisms involved in acid-base balance
• Describe the respiratory and metabolic acid-base disorders

151 151