1. Acid-Base Balance

2. Table 27-3 A Review of Important Terms Relating to Acid–Base Balance

3. 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

4. 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 4

6. pH and enzyme function
Hydrogen ion concentration has a widespread effect on the function of the body's enzyme systems.
The hydrogen ion is highly reactive and will combine with bases or negatively charged ions at very low concentrations.
Proteins contain many negatively charged and basic groups within their structure.
Thus, a change in pH will alter the degree ionization of a protein, which may in turn affect its functioning.
At more extreme hydrogen ion concentrations a protein's structure may be completely disrupted (the protein is then said to be denatured).

7. 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

8. Types of acids in the body
Volatile acid comes from carbohydrate and fat metabolism
Can leave solution and enter the atmosphere (e.g. carbonic acid – H2CO3)
Breaks in the lungs to carbon dioxide and water
In the tissues CO2 reacts with water to form carbonic acid, which dissociate to give hydrogen ions and bicarbonate ions
This reaction occurs spontaneously, but happens faster with the presence of carbonic anhydrase (CA)
PCO2 and pH are inversely related
CO2 + H20  H2CO3  HCO3- + H+

9. Types of acids in the body
Fixed acids
Acids that do not leave solution (e.g. sulfuric and phosphoric acids – produced during catabolism of amino acids)
Eliminated by the kidneys
Organic acids
by-products of anerobic metabolism such as lactic acid, ketone bodies

10. Hydrogen ion and pH balance in the body
Acid-Base Balance
Hydrogen ion and pH balance in the body
CO2 (+ H2O) Lactic acid Ketoacids
Fatty acids Amino acids
H+ input
Plasma pH 7.38–7.42
Buffers: • HCO3– in extracellular fluid • Proteins, hemoglobin, phosphates in cells • Phosphates, ammonia in urine
CO2 (+ H2O)
H+ output H+
Figure 20-18

11. Buffers
Buffers - compound that limits the change in hydrogen ion concentration (and so pH) when hydrogen ions are added or removed from the solution.

12. Buffer systems Two types of buffer in the body Chemical buffers
Bicarbonate, phosphate and protein systems
Substance that binds H+ and remove it from the solution if its concentration rises or release it if concentration decreases
Fast reaction within seconds
Physiological
respiratory (fast reaction – few minutes) or urinary (slow reaction – hours to days)
Regulates pH by controlling the body’s output of bases, acids or CO2

13. 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 13

14. Chemical Buffer Systems
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

15. 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
CO2 + H2O  H2CO3  H+ + HCO3¯

16. 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 16

17. Figure 27-9 The Basic Relationship between PCO2 and Plasma pH
40–45
mm Hg
HOMEOSTASIS
If PCO2 rises
H2O 
CO2
H2CO3
HCO3 H
When carbon dioxide levels rise, more carbonic acid
forms, additional hydrogen ions and bicarbonate ions
are released, and the pH goes down.
PCO2 pH 17

18. Figure 27-9 The Basic Relationship between PCO2 and Plasma 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. pH
PCO2 18

19. 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

20. 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

21. Figure 27-11 The Role of Amino Acids in Protein Buffer Systems
Neutral pH
If pH rises
If pH falls
In alkaline medium, amino
acid acts as an acid
and releases H
Amino acid
In acidic medium, amino
acid acts as a base
and absorbs H 21

22. Buffer Systems in Body Fluids
Figure 27.7

23. Figure 27-10 Buffer Systems in Body Fluids
occur in
Intracellular fluid (ICF)
Extracellular fluid (ECF)
Phosphate Buffer
System
Protein Buffer Systems
Carbonic Acid–
Bicarbonate Buffer
System
Protein buffer systems contribute to the regulation
of pH in the ECF and ICF. These buffer systems interact
extensively with the other two buffer systems.
The phosphate
buffer system
has an important
role in buffering
the pH of the ICF
and of urine.
The carbonic acid–
bicarbonate buffer
system is most
important in the ECF.
Hemoglobin buffer
system (RBCs only)
Amino acid buffers
(All proteins)
Plasma protein
buffers 23

24. Physiological Buffer Systems – respiratory system
The respiratory system regulation of acid-base balance is a physiological buffering system
The respiratory buffering system takes care of volatile acids – by-products of glucose and fat metabolism
CO2 + H2O  H2CO3  H+ + HCO3¯

25. Physiological Buffer Systems – respiratory system
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

26. Physiological Buffer Systems – kidneys
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 excrete 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

27. Physiological Buffer Systems – kidneys
The kidney takes care of the non-volatile acid products
By-products of protein metabolism and anaerobic respiration
The kidneys must prevent the loss of bicarbonate ions (re-absorb) that is being constantly filtered from the blood.
Both tasks are accomplished by secretion of hydrogen ions
Only about 10% of the hydrogen ions secreted will be excreted
As a result of the H+ excretion the urine is usually acidic

28. Reabsorption of Bicarbonate
In a person with normal acid-base balance all the HCO3- in the tubular fluid is consumed by neutralizing H+ - no HCO3- in the urine
HCO3- molecules are filtered by the glomerulus and than reabsorbed and appear in the peritubular capillary (most in the PCT).
The re-absorption is not direct – the luminar surface of the tubular cells can not absorb HCO3-
The kidney cells can also generate new HCO3- if needed

29. Buffers in Urine
The ability to eliminate large numbers of H+ in a normal volume of urine depends on the presence of buffers in urine
Carbonic acid–bicarbonate buffer system
Phosphate buffer system
Ammonia buffer system

30. Renal Responses to Acidosis
Secretion of H+
Activity of buffers in tubular fluid
Removal of CO2
Reabsorption of NaHCO3–

31. Renal Responses to Alkalosis
Rate of secretion at kidneys declines
Tubule cells do not reclaim bicarbonates in tubular fluid
Collecting system transports HCO3– into tubular fluid while releasing strong acid (HCl) into peritubular fluid

32. Acid–Base Balance Disturbances
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

33. Respiratory Acidosis and Alkalosis
Result from failure of the respiratory system to balance pH
PCO2 is the most important indicator of respiratory inadequacy
PCO2 levels
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

34. Respiratory Acidosis and Alkalosis
Respiratory acidosis is the most common cause of acid-base imbalance
Occurs when a person breathes shallowly, or gas exchange is slowed down by diseases such as pneumonia, cystic fibrosis, or emphysema
Respiratory alkalosis is a common result of hyperventilation

35. Figure 27-15a Respiratory Acid–Base Regulation
Responses to Acidosis
Respiratory compensation:
Stimulation of arterial and CSF chemo-
receptors results in increased
respiratory rate.
Increased
PCO2
Renal compensation:
Combined Effects
H ions are secreted and HCO3
ions are generated.
Respiratory Acidosis
Decreased PCO2
Elevated PCO2 results
in a fall in plasma pH
Buffer systems other than the carbonic
acid–bicarbonate system accept H ions.
Decreased H and
increased HCO3
HOMEOSTASIS
DISTURBED
HOMEOSTASIS
RESTORED
HOMEOSTASIS
Hypoventilation
causing increased PCO2
Plasma pH
returns to normal
Normal
acid–base
balance
Respiratory acidosis 35

36. Figure 27-15b Respiratory Acid–Base Regulation
HOMEOSTASIS
HOMEOSTASIS
DISTURBED
HOMEOSTASIS
RESTORED
Normal
acid–base
balance
Hyperventilation
causing decreased PCO2
Plasma pH
returns to normal
Respiratory Alkalosis
Combined Effects
Responses to Alkalosis
Lower PCO2 results
in a rise in plasma pH
Increased PCO2
Respiratory compensation:
Inhibition of arterial and CSF
chemoreceptors results in a decreased
respiratory rate.
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.
Respiratory alkalosis 36

37. Metabolic Acidosis
Metabolic acidosis is the second most common cause of acid-base imbalance
Can be a result of:
Failure of the kidney to excrete metabolic acids
Renal acidosis is either the inability of kidney to excrete H+ or to re- absorb bicarbonate ion
Diarrhea – most common reason of metabolic acidosis
Loss of large amounts of sodium bicarbonate in the feces (which is normal component of the feces)
Diabetes mellitus – results in breakdown of fat that releases acids
Ingestion of acids
Acetylsalicylic acid (aspirin)
Methyl alcohol (forms acid when metabolized)

38. Is caused by elevated HCO3– concentrations
Metabolic Alkalosis
Is caused by elevated HCO3– concentrations
Bicarbonate ions interact with H+ in solution
Forming H2CO3
Reduced H+ causes 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

39. 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 39

40. 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 40

41. Acid-Base Balance
Table 20-2

42. The response to acidosis caused by the addition of H
Start
CARBONIC ACID-BICARBONATE BUFFER SYSTEM
BICARBONATE RESERVE
CO2
CO2  H2O
H2CO3 H 
HCO3
HCO3 
Na
NaHCO3
(carbonic acid)
(bicarbonate ion)
(sodium bicarbonate)
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.
Kidney tubules respond by (1) secreting H
ions, (2) removing CO2, and (3) reabsorbing
HCO3 to help replenish the bicarbonate
reserve.
Secretion
of H 42

43. The response to alkalosis caused by the removal of H
Start
CARBONIC ACID-BICARBONATE BUFFER SYSTEM
BICARBONATE RESERVE
Lungs
CO2 
H2O
H2CO3 H 
HCO3
HCO3 
Na
NaHCO3
(carbonic acid)
(bicarbonate ion)
(sodium bicarbonate)
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
Kidney tubules respond by
conserving H ions and
secreting HCO3.
Secretion
of HCO3 43