1. Homeostasis

2. 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+

3. The major factors involved in the maintenance of acid-base balance
The respiratory system plays a key role by eliminating carbon dioxide.
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.
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
Figure 24 Section 2.1 Acid-Base Balance
Buffer Systems
Buffer systems can temporarily store H and thereby provide short-term pH stability.
Figure 24 Section 3

4. 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

5. Section 2: Acid-Base Balance
Classes of acids (continued)
Volatile acids
Can leave body by external respiration
Example: carbonic acid (H2CO3)

6. 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

7. Figure 24.5.1 Potentially dangerous disturbances in acid-base balance are opposed by buffer systems7

8. Extremely acidic Extremely basic
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
Figure Potentially dangerous disturbances in acid-base balance are opposed by buffer systems
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 8

9. 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

10. The inverse relationship between the PCO2 and pH
PCO2 40–45 mm Hg
pH 7.35–7.45
HOMEOSTASIS
If PCO2 rises
If PCO2 falls
H2O  CO2
H2CO3
H  HCO3
H  HCO3
H2CO3
H2O  CO2
When carbon dioxide levels rise, more carbonic acid forms, additional hydrogen ions and bicarbonate ions are released, and the pH goes down.
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 Potentially dangerous disturbances in acid-base balance are opposed by buffer systems
PCO2 pH pH
PCO2
Figure 10

11. Module 24.5: Buffer systems
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

12. 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.
Adding H to the solution upsets the equilibrium and results in the formation of additional molecules of the weak acid.
Removing H from the solution also upsets the equilibrium and results in the dissociation of additional molecules of HY. This releases H.
H  Y H
H  HY
H  HY H
H  Y HY
H  Y
Figure Potentially dangerous disturbances in acid-base balance are opposed by buffer systems
Figure 12

13. 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.

14. Module 24.6: Major body buffer systems
Three major body buffer systems
All can only temporarily affect pH (H+ not eliminated)
Phosphate buffer system
Buffers pH of ICF and urine
Carbonic acid–bicarbonate buffer system
Most important in ECF
Fully reversible
Bicarbonate reserves (from NaHCO3 in ECF) contribute

15. Module 24.6: Major body buffer systems
Three major body buffer systems (continued)
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

16. Buffer Systems The body’s three major buffer systems
occur in
Intracellular fluid (ICF)
Extracellular fluid (ECF)
Phosphate Buffer System
Protein Buffer Systems
Carbonic Acid– Bicarbonate Buffer System
Contribute to the regulation of pH in the ECF and ICF; interact extensively with the other two buffer systems
Has an important role in buffering the pH of the ICF and of urine
Is most important in the ECF
Figure Buffer systems can delay but not prevent pH shifts in the ICF and ECF
Hemoglobin buffer system (RBCs only)
Amino acid buffers (All proteins)
Plasma protein buffers
Figure 16

17. CARBONIC ACID–BICARBONATE BUFFER SYSTEM
The reactions of the carbonic acid–bicarbonate buffer system
BICARBONATE RESERVE
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.
CARBONIC ACID–BICARBONATE BUFFER SYSTEM
CO2
CO2  H2O
H2CO3 (carbonic acid) H
 HCO3
HCO3  Na
NaHCO3 (sodium bicarbonate)
(bicarbonate ion)
Lungs
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 Buffer systems can delay but not prevent pH shifts in the ICF and ECF
Addition of H from metabolic activity
Start
Figure 17

18. Released with exhalation
The events involved in the functioning of the hemoglobin buffer system
Tissue cells
Plasma
Plasma
Lungs
Red blood cells
Red blood cells
Released with exhalation
H2O
H2O
CO2
H2CO3
HCO3  Hb H Hb
H  HCO3
H2CO3
CO2
Figure Buffer systems can delay but not prevent pH shifts in the ICF and ECF
Figure 18

19. The mechanism by free amino acids function in protein buffer systems
Start
Increasing acidity (decreasing pH)
Normal 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 Buffer systems can delay but not prevent pH shifts in the ICF and ECF
Figure 19

20. 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

21. 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.

22. Module 24.7: 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

23. NaHCO3 (sodium bicarbonate) Other buffer systems absorb H
The responses to metabolic acidosis
Addition of H
Start
CARBONIC ACID–BICARBONATE BUFFER SYSTEM
BICARBONATE RESERVE
CO2
CO2  H2O
H2CO3 (carbonic acid) H
 HCO3
HCO3  Na
NaHCO3 (sodium bicarbonate)
(bicarbonate ion)
Lungs
Generation of HCO3
Respiratory Response to Acidosis
Other buffer systems absorb H
KIDNEYS
Renal Response to Acidosis
Increased respiratory rate lowers PCO2, effectively converting carbonic acid molecules to water.
Figure The homeostatic responses to metabolic acidosis and alkalosis involve respiratory and renal mechanisms as well as buffer systems
Kidney tubules respond by (1) secreting H ions, (2) removing CO2, and (3) reabsorbing HCO3 to help replenish the bicarbonate reserve.
Secretion of H
Figure 23

24. The activity of renal tubule cells in CO2 removal and HCO3 production
Tubular fluid
Renal tubule cells
ECF
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.
CO2
CO2  H2O
CO2
Carbonic anhydrase
Na
Carbonic anhydrase converts CO2 and water to carbonic acid, which then dissociates. H
H2CO3 H H
HCO3
HCO3
Cl
The chloride ions exchanged for bicarbonate ions are excreted in the tubular fluid. H
Cl
HCO3
Na
Bicarbonate ions and sodium ions are transported into the ECF, adding to the bicarbonate reserve.
Figure The homeostatic responses to metabolic acidosis and alkalosis involve respiratory and renal mechanisms as well as buffer systems
Figure 24

25. 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

26. 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
HCO3– secreted into urine (in exchange for Cl–)
H+ actively reabsorbed into ECF

27. NaHCO3 (sodium bicarbonate) Other buffer systems release H
The responses to metabolic alkalosis
Removal of H
Start
CARBONIC ACID–BICARBONATE BUFFER SYSTEM
BICARBONATE RESERVE
Lungs
CO2  H2O
H2CO3 (carbonic acid) H
 HCO3
HCO3  Na
NaHCO3 (sodium bicarbonate)
(bicarbonate ion)
Generation of H
Respiratory Response to Alkalosis
Other buffer systems release H
KIDNEYS
Decreased respiratory rate elevates PCO2, effectively converting CO2 molecules to carbonic acid.
Renal Response to Alkalosis
Figure The homeostatic responses to metabolic acidosis and alkalosis involve respiratory and renal mechanisms as well as buffer systems
Kidney tubules respond by conserving H ions and secreting HCO3.
Secretion of HCO3
Figure 27

28. CO2 generated by the tubule cell is added to the CO2 diffusing into the cell from the tubular fluid and from the ECF.
The events in the secretion of bicarbonate ions into the tubular fluid along the PCT, DCT, and collecting system
Tubular fluid
Renal tubule cells
ECF
CO2
CO2  H2O
CO2
Carbonic anyhydrase converts CO2 and water to carbonic acid, which then dissociates.
Carbonic anhydrase
H2CO3
HCO3
HCO3 H H
The hydrogen ions are actively transported into the ECF, accompanied by the diffusion of chloride ions.
Cl
Cl
Figure The homeostatic responses to metabolic acidosis and alkalosis involve respiratory and renal mechanisms as well as buffer systems
HCO3 is pumped into the tubular fluid in exchange for chloride ions that will diffuse into the ECF.
Figure 28

29. 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?

30. CLINICAL MODULE 24.8: 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+)

31. CARBONIC ACID–BICARBONATE BUFFER SYSTEM NaHCO3 (sodium bicarbonate)
The events in respiratory acidosis
CARBONIC ACID–BICARBONATE BUFFER SYSTEM
BICARBONATE RESERVE
CO2
CO2  H2O
H2CO2 (carbonic acid) H
 HCO3
HCO3  Na
NaHCO3 (sodium bicarbonate)
(bicarbonate ion)
Lungs
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.
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.
As bicarbonate ions and hydrogen ions are released through the dissociation of carbonic acid, the excess bicarbonate ions become part of the bicarbonate reserve.
Figure Respiratory acid-base disorders are the most common challenges to acid-base balance
Figure 31

32. HOMEOSTASIS Responses to Acidosis
The integrated homeostatic responses to respiratory acidosis
Respiratory compensation
Stimulation of arterial and CSF chemoreceptors results in increased respiratory rate.
Increased PCO2
Renal compensation
H ions are secreted and HCO3 ions are generated.
Combined Effects
Respiratory Acidosis
Decreased PCO2
Buffer systems other than the carbonic acid–bicarbonate system accept H ions.
Elevated PCO2 results in a fall in plasma pH
Decreased H and increased HCO3
HOMEOSTASIS DISTURBED
HOMEOSTASIS RESTORED
Figure Respiratory acid-base disorders are the most common challenges to acid-base balance
HOMEOSTASIS
Hypoventilation causing increased PCO2
Plasma pH returns to normal
Start
Normal acid- base balance
Figure 32

33. 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+)

34. CARBONIC ACID–BICARBONATE BUFFER SYSTEM NaHCO3 (sodium bicarbonate)
The events in respiratory alkalosis
CARBONIC ACID–BICARBONATE BUFFER SYSTEM
BICARBONATE RESERVE
CO2
CO2  H2O
H2CO2 (carbonic acid) H
 HCO3
HCO3  Na
NaHCO3 (sodium bicarbonate)
(bicarbonate ion)
Lungs
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.
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 Respiratory acid-base disorders are the most common challenges to acid-base balance
Figure 34

35. The integrated homeostatic responses to respiratory alkalosis
HOMEOSTASIS
HOMEOSTASIS DISTURBED
Start
HOMEOSTASIS RESTORED
Normal acid- base balance
Hyperventilation causing decreased PCO2
Plasma pH returns to normal
Combined Effects
Respiratory Alkalosis
Responses to Alkalosis
Increased PCO2
Lower PCO2 results in a rise in plasma pH
Respiratory compensation
Inhibition of arterial and CSF chemoreceptors results in a decreased respiratory rate.
Increased H and decreased HCO3
Figure Respiratory acid-base disorders are the most common challenges to acid-base balance
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 35

36. 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?