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Homeostasis
Section 2: Acid-Base Balance
• Acid-base balance (H+ production = loss)
– Normal plasma pH: 7.35–7.45
– H+ gains: many metabolic activities produce
acids
•
•
CO2 (to carbonic acid) from aerobic respiration
Lactic acid from glycolysis
– H+ losses and storage
•
•
•
Respiratory system eliminates CO2
H+ excretion from kidneys
Buffers temporarily store H+
The major factors involved in the maintenance
of acid-base balance
The respiratory system
plays a key role by
eliminating
carbon dioxide.
Active tissues
continuously generate
carbon dioxide, which in
solution forms carbonic
acid. Additional acids,
such as lactic acid, are
produced in the course of
normal metabolic
operations.
Normal
plasma pH
(7.35–7.45)
Tissue cells
Buffer Systems
The kidneys play a major
role by secreting
hydrogen ions into the
urine and generating
buffers that enter the
bloodstream. The rate of
excretion rises and falls
as needed to maintain
normal plasma pH. As a
result, the normal pH of
urine varies widely but
averages 6.0—slightly
acidic.
Buffer systems can
temporarily store H
and thereby provide
short-term pH
stability.
Figure 24 Section 2 1
Section 2: Acid-Base Balance
• Classes of acids
– Fixed acids
•
Do not leave solution
–
•
Remain in body fluids until kidney excretion
Examples: sulfuric and phosphoric acid
–
Generated during catabolism of amino acids, phospholipids, and
nucleic acids
– Organic acids
•
Part of cellular metabolism
–
•
Examples: lactic acid and ketones
Most metabolized rapidly so no accumulation
Section 2: Acid-Base Balance
• Classes of acids (continued)
– Volatile acids
•
•
Can leave body by external respiration
Example: carbonic acid (H2CO3)
Module 24.5: Buffer systems
• pH imbalance
– ECH pH normally between 7.35 and 7.45
• Acidemia (plasma pH <7.35): acidosis (physiological state)
– More common due to acid-producing metabolic activities
– Effects
» CNS function deteriorates, may cause coma
» Cardiac contractions grow weak and irregular
» Peripheral vasodilation causes BP drop
• Alkalemia (plasma pH >7.45): alkalosis (physiological state)
– Can be dangerous but relatively rare
Figure 24.5 1
The narrow range of normal pH of the ECF, and the conditions that result from pH shifts outside the normal range
The pH of the ECF
(extracellular fluid)
normally ranges from
7.35 to 7.45.
When the pH of plasma falls below
7.5, acidemia exists. The
physiological state that results is
called acidosis.
When the pH of plasma rises
above 7.45, alkalemia exists.
The physiological state that
results is called alkalosis.
Extremely
acidic
Extremely
basic
pH
Severe acidosis (pH below 7.0) can be deadly
because (1) central nervous system function
deteriorates, and the individual may become
comatose; (2) cardiac contractions grow weak and
irregular, and signs and symptoms of heart failure
may develop; and (3) peripheral vasodilation
produces a dramatic drop in blood pressure,
potentially producing circulatory collapse.
Severe alkalosis is also
dangerous, but serious cases
are relatively rare.
Figure 24.5 2
Module 24.5: Buffer systems
• CO2 partial pressure effects on pH
– Most important factor affecting body pH
– H2O + CO2  H2CO3  H+ + HCO3–
• Reversible reaction that can buffer body pH
– Adjustments in respiratory rate can affect body pH
The inverse relationship between the PCO2 and pH
PCO2
40–45
mm Hg
If PCO2 rises
H2O  CO2
H2CO3
H  HCO3
When carbon dioxide levels rise, more carbonic acid
forms, additional hydrogen ions and bicarbonate ions
are released, and the pH goes down.
pH
7.35–7.45
HOMEOSTASIS
If PCO2 falls
H  HCO3
H2CO3
H2O  CO2
When the PCO2 falls, the reaction runs in reverse, and
carbonic acid dissociates into carbon dioxide and
water. This removes H ions from solution and
increases the pH.
Figure 24.5 3
Module 24.5: Buffer systems
• Buffer
– Substance that opposes changes to pH by removing
or adding H+
– Generally consists of:
• Weak acid (HY)
• Anion released by its dissociation (Y–)
• HY  H+ + Y– and H+ + Y–  HY
The reactions that occur when pH buffer systems function
A buffer system in body fluids generally
consists of a combination of a weak acid (HY)
and the anion (Y) released by its dissociation.
The anion functions as a weak base. In solution,
molecules of the weak acid exist in equilibrium
with its dissociation products.
HY
H

Y
Adding H to the
solution upsets the
equilibrium and results
in the formation of
additional molecules of
the weak acid.
H  Y
H
H  HY
Removing H from the
solution also upsets the
equilibrium and results
in the dissociation of
additional molecules of
HY. This releases H.
H  HY
H  Y
H
Figure 24.5 4
Module 24.5 Review
a. Define acidemia and
alkalemia.
b. What is the most
important factor affecting
the pH of the ECF?
c. Summarize the
relationship between CO2
levels and pH.
Module 24.6: Major body buffer systems
•
Three major body buffer systems
–
All can only temporarily affect pH (H+ not eliminated)
1.
Phosphate buffer system
•
2.
Buffers pH of ICF and urine
Carbonic acid–bicarbonate buffer system
•
•
•
Most important in ECF
Fully reversible
Bicarbonate reserves (from NaHCO3 in ECF) contribute
Module 24.6: Major body buffer systems
• Three major body buffer systems (continued)
3. Protein buffer systems (in ICF and ECF)
•
Usually operate under acid conditions (bind H+)
–
•
Binding to carboxyl group (COOH–) and amino group (—NH2)
Examples:
–
–
–
Hemoglobin buffer system
» CO2 + H2O  H2CO3  HCO3– + Hb-H+
» Only intracellular system with immediate effects
Amino acid buffers (all proteins)
Plasma proteins
The body’s three major buffer systems
Buffer Systems
occur in
Intracellular fluid (ICF)
Phosphate Buffer
System
Has an important
role in buffering the
pH of the ICF and
of urine
Extracellular fluid (ECF)
Carbonic Acid–
Bicarbonate Buffer
System
Protein Buffer Systems
Contribute to the regulation of pH in the ECF and ICF;
interact extensively with the other two buffer systems
Is most important in the
ECF
Hemoglobin
buffer system
(RBCs only)
Amino acid
buffers
(All proteins)
Plasma
protein
buffers
Figure 24.6 1
BICARBONATE RESERVE
The reactions of the carbonic acid–bicarbonate buffer system
CARBONIC ACID–BICARBONATE
BUFFER SYSTEM
CO2
Lungs
CO2  H2O
H2CO3
(carbonic acid)
Start
H
 HCO3
(bicarbonate ion)
Addition of H
from metabolic
activity
Body fluids contain a large reserve of
HCO3, primarily in the form of dissolved
molecules of the weak base sodium
bicarbonate (NaHCO3). This readily
available supply of HCO3 is known as
the bicarbonate reserve.
HCO3  Na
NaHCO3
(sodium bicarbonate)
The primary function of the carbonic
acid–bicarbonate buffer system is to
protect against the effects of the organic
and fixed acids generated through
metabolic activity. In effect, it takes the H
released by these acids and generates
carbonic acid that dissociates into water
and carbon dioxide, which can easily be
eliminated at the lungs.
Figure 24.6 4
The events involved in the functioning of the hemoglobin buffer system
Tissue
cells
Plasma
Lungs
Plasma
Red blood cells
Red blood cells
H2O
H2O
CO2
H2CO3
HCO3  Hb
H
Hb
H  HCO3
H2CO3
Released
with
exhalation
CO2
Figure 24.6 2
Start
The mechanism by free amino acids function in
protein buffer systems
Normal pH
Increasing acidity (decreasing pH)
(7.35–7.45)
At the normal pH of
body fluids (7.35–
7.45), the carboxyl
groups of most amino
acids have released
their hydrogen ions.
If pH drops, the carboxylate ion (COO)
and the amino group (—NH2) of a free
amino acid can act as weak bases and
accept additional hydrogen ions, forming a
carboxyl group (—COOH) and an amino
ion (—NH3), respectively. Many of the
R-groups can also accept hydrogen ions,
forming RH.
Figure 24.6 3
Module 24.6: Major body buffer
systems
• Disorders
– Metabolic acid-base disorders
•
•
Production or loss of excessive amounts of fixed or
organic acids
Carbonic acid–bicarbonate system works to counter
– Respiratory acid-base disorders
•
•
Imbalance of CO2 generation and elimination
Must be corrected by depth and rate of respiration
changes
Module 24.6 Review
a. Identify the body’s three
major buffer systems.
b. Describe the carbonic
acid–bicarbonate buffer
system.
c. Describe the roles of the
phosphate buffer
system.
Module 24.7: Metabolic acid-base
disorders
•
Metabolic acid-base disorders
–
Metabolic acidosis
•
•
Develops when large numbers of H+ are released by organic or fixed
acids
Accommodated by respiratory and renal responses
–
–
Respiratory response
»
Increased respiratory rate lowers PCO2
»
H+ + HCO3–  H2CO3  H2O + CO2
Renal response
»
Occurs in PCT, DCT, and collecting system
»
H2O + CO2  H2CO3  H+ + HCO3–
 H+ secreted into urine
 HCO3– reabsorbed into ECF
The responses to metabolic acidosis
Start
Addition
of H
CARBONIC ACID–BICARBONATE BUFFER SYSTEM
CO2
CO2  H2O
Lungs
Respiratory Response
to Acidosis
Increased respiratory
rate lowers PCO2,
effectively converting
carbonic acid molecules
to water.
H2CO3
(carbonic acid)
Other
buffer
systems
absorb H
H
 HCO3
(bicarbonate ion)
KIDNEYS
BICARBONATE RESERVE
HCO3  Na
NaHCO3
(sodium bicarbonate)
Generation
of HCO3
Renal Response to Acidosis
Secretion
of H
Kidney tubules respond by (1) secreting H
ions, (2) removing CO2, and (3) reabsorbing
HCO3 to help replenish the bicarbonate
reserve.
Figure 24.7 1
The activity of renal
tubule cells in CO2
removal and HCO3
production
Tubular
fluid
CO2
H
H
ECF
Renal tubule cells
Carbonic
Na anhydrase
CO2

H2O
CO2
H2CO3
H
HCO3
HCO3
Cl
H
Cl
HCO3
Na
Steps in CO2 removal and
HCO3 production
CO2 generated by the tubule
cell is added to the CO2
diffusing into the cell from
the urine and from the ECF.
Carbonic anhydrase
converts CO2 and water to
carbonic acid, which then
dissociates.
The chloride ions exchanged
for bicarbonate ions are
excreted in the tubular fluid.
Bicarbonate ions and
sodium ions are transported
into the ECF, adding to the
bicarbonate reserve.
Figure 24.7 2
Module 24.7: Metabolic acid-base
disorders
• Metabolic alkalosis
– Develops when large numbers of H+ are removed
from body fluids
–
–
–
Rate of kidney H+ secretion declines
Tubular cells do not reclaim bicarbonate
Collecting system transports bicarbonate into urine and retains
acid (HCl) in ECF
Module 24.7: Metabolic acid-base
disorders
• Metabolic alkalosis (continued)
– Accommodated by respiratory and renal responses
•
Respiratory response
–
–
•
Decreased respiratory rate raises PCO2
H2O + CO2  H2CO3  H+ + HCO3–
Renal response
–
–
Occurs in PCT, DCT, and collecting system
H2O + CO2  H2CO3  H+ + HCO3–
» HCO3– secreted into urine (in exchange for Cl–)
» H+ actively reabsorbed into ECF
The responses to metabolic alkalosis
Start
Removal
of H
CARBONIC ACID–BICARBONATE BUFFER SYSTEM
Lungs
CO2  H2O
Respiratory Response
to Alkalosis
Decreased respiratory
rate elevates PCO2,
effectively converting
CO2 molecules to
carbonic acid.
H2CO3
(carbonic acid)
Other
buffer
systems
release H
H
 HCO3
(bicarbonate ion)
Generation
of H
BICARBONATE RESERVE
HCO3  Na
NaHCO3
(sodium bicarbonate)
KIDNEYS
Renal Response to Alkalosis
Secretion
of HCO3
Kidney tubules respond by
conserving H ions and
secreting HCO3.
Figure 24.7 3
The events in the
secretion of bicarbonate
ions into the tubular
fluid along the PCT, DCT,
and collecting system
Tubular
fluid
Renal tubule cells
CO2

H2O
CO2
ECF
CO2 generated by the tubule
cell is added to the CO2
diffusing into the cell from the
tubular fluid and from the ECF.
CO2
Carbonic anyhydrase converts
CO2 and water to carbonic
acid, which then dissociates.
Carbonic
anhydrase
H2CO3
HCO3
HCO3
Cl
H
H
Cl
The hydrogen ions are actively
transported into the ECF,
accompanied by the diffusion
of chloride ions.
HCO3 is pumped into the
tubular fluid in exchange for
chloride ions that will diffuse
into the ECF.
Figure 24.7 4
Module 24.7 Review
a. Describe metabolic acidosis.
b. Describe metabolic alkalosis.
c. lf the kidneys are conserving HCO3– and
eliminating H+ in acidic urine, which is
occurring: metabolic alkalosis or metabolic
acidosis?
CLINICAL MODULE 24.8: Respiratory
acid-base disorders
•
Respiratory acid-base disorders
–
Respiratory acidosis
•
•
•
CO2 generation outpaces rate of CO2 elimination at lungs
Shifts bicarbonate buffer system toward generating more carbonic
acid
H2O + CO2  H2CO3  H+ + HCO3–
–
–
HCO3– goes into bicarbonate reserve
H+ must be neutralized by any of the buffer systems
» Respiratory (increased respiratory rate)
» Renal (H+ secreted and HCO3– reabsorbed)
» Proteins (bind free H+)
The events in respiratory acidosis
CARBONIC ACID–BICARBONATE
BUFFER SYSTEM
CO2
Lungs
CO2  H2O
H2CO2
(carbonic acid)
When respiratory activity does not keep
pace with the rate of CO2 generation,
alveolar and plasma PCO2 increases.
This upsets the equilibrium and drives
the reaction to the right, generating
additional H2CO3, which releases H
and lowers plasma pH.
H
 HCO3
(bicarbonate ion)
As bicarbonate ions and hydrogen ions
are released through the dissociation of
carbonic acid, the excess bicarbonate
ions become part of the bicarbonate
reserve.
BICARBONATE RESERVE
HCO3  Na
NaHCO3
(sodium bicarbonate)
To limit the pH effects of
respiratory acidosis, the excess
H must either be tied up by
other buffer systems or excreted
at the kidneys. The underlying
problem, however, cannot be
eliminated without an increase in
the respiratory rate.
Figure 24.8 1
Responses to Acidosis
The integrated homeostatic responses
to respiratory acidosis
Increased
PCO2
Respiratory compensation
Stimulation of arterial and CSF
chemoreceptors results in
increased respiratory rate.
Renal compensation
H ions are secreted and
HCO3 ions are generated.
Combined Effects
Respiratory Acidosis
Elevated PCO2 results
in a fall in plasma pH
Decreased PCO2
Buffer systems other than the
carbonic acid–bicarbonate
system accept H ions.
Decreased H and
increased HCO3
HOMEOSTASIS
RESTORED
HOMEOSTASIS
DISTURBED
Hypoventilation
causing increased PCO2
HOMEOSTASIS
Normal acidbase balance
Start
Plasma pH
returns to normal
Figure 24.8 2
CLINICAL MODULE 24.8: Respiratory
acid-base disorders
•
Respiratory alkalosis
–
–
CO2 elimination at lungs outpaces CO2 generation rate
Shifts bicarbonate buffer system toward generating more carbonic
acid
H+ + HCO3–  H2CO3  H2O + CO2
–
•
–
H+ removed as CO2 exhaled and water formed
Buffer system responses
–
–
–
Respiratory (decreased respiratory rate)
Renal (HCO3– secreted and H+ reabsorbed)
Proteins (release free H+)
The events in respiratory alkalosis
CARBONIC ACID–BICARBONATE
BUFFER SYSTEM
CO2
Lungs
CO2  H2O
H2CO2
(carbonic acid)
If respiratory activity exceeds the rate of CO2
generation, alveolar and plasma PCO2 decline,
and this disturbs the equilibrium and drives
the reactions to the left, removing H and
elevating plasma pH.
H
 HCO3
(bicarbonate ion)
BICARBONATE RESERVE
HCO3  Na
NaHCO3
(sodium bicarbonate)
As bicarbonate ions and hydrogen
ions are removed in the formation of
carbonic acid, the bicarbonate ions—
but not the hydrogen ions—are
replaced by the bicarbonate reserve.
Figure 24.8 3
The integrated homeostatic responses to
respiratory alkalosis
HOMEOSTASIS
HOMEOSTASIS
DISTURBED
Start
Normal acidbase balance
HOMEOSTASIS
RESTORED
Plasma pH
returns to normal
Hyperventilation
causing decreased PCO2
Respiratory Alkalosis
Responses to Alkalosis
Lower PCO2 results
in a rise in plasma pH
Respiratory compensation
Inhibition of arterial and CSF
chemoreceptors results in a
decreased respiratory rate.
Combined Effects
Increased PCO2
Increased H and
decreased HCO3
Renal compensation
Decreased
PCO2
H ions are generated and
HCO3 ions are secreted.
Buffer systems other than the
carbonic acid–bicarbonate system
release H ions.
Figure 24.8 4
CLINICAL MODULE 24.8 Review
a. Define respiratory acidosis
and respiratory alkalosis.
b. What would happen to the
plasma PCO2 of a patient
who has an airway
obstruction?
c. How would a decrease in
the pH of body fluids
affect the respiratory
rate?