1. Blood Gases, pH and Buffer system
Part 1

2. Introduction
An important aspect of clinical chemistry is information on a patient's acid-base balance and blood gas homeostasis.
These data often are used to assess patients in life-threatening situations.
This lecture discusses:
the body's mechanisms to maintain acid-base balance and
exchange of gases, carbon dioxide and oxygen,
M. Zaharna Clin. Chem. 2015

3. Definitions: Acid, Base, Buffer
a substance that yields H+ ions in H2O.
Base:
a substance that yields a hydroxyl ion (OH-).
Buffer:
the combination of a weak acid and its salt, is a system that resists changes in pH.
M. Zaharna Clin. Chem. 2015

4. Acid, Base, Buffer
The relative strengths of acids and bases, their ability to dissociate in water, are described by their dissociation constant (ionization constant - K value)
pK: defined as the negative log of the ionization constant;
that is pH where the protonated and unprotonated forms are present in equal concentration.
M. Zaharna Clin. Chem. 2015

5. Strong acids vs. Strong Base
have pK value of less than 3.0
Strong base:
have a pK value greater than 9.0
M. Zaharna Clin. Chem. 2015

6. Acid-Base balance Maintenance of hydrogen ions:
Body produces mmol of H/day,
normal concentration of H in ECF ranges from nmol (pH, )
Any deviation from the values the body will try to compensate.
>44 nmol/L: altered consciousness, coma- death
<36 nmol/L: neuromuscular irritability, tetany, loss of consciousness- death.
M. Zaharna Clin. Chem. 2015

7. Acid-Base balance Because pH is the negative log of the cH+
Decrease in H+ ion Increase pH
Increase H + ions Decrease pH
Arterial blood pH is controlled by:
Buffers
Respiratory System
and Kidneys
C= concentration
C= concentration
M. Zaharna Clin. Chem. 2015

8. Buffer System: Regulation of H+
First line of defense to changes in H+ consist of:
weak acid (H2CO3) & its salt (HCO3-)
Add acid to H2CO3 & HCO3- system:
the HCO3- combines with H from the acid to form H2CO3.
Add a base to the system:
H2CO3 combines with OH to form H2O and HCO3
Keeps the body at the correct pH ( )
M. Zaharna Clin. Chem. 2015

9. Buffer System: Regulation of H+
Bicarbonate – carbonic acid system has low buffering capacity but still an important buffer system for 3 reasons:
H2CO3 dissociates into CO2 & H2O allowing H+ to be eliminated as CO2 by lungs
Changes in CO2 modify the ventilation rate
HCO3- conc. can be altered by the kidneys
M. Zaharna Clin. Chem. 2015

10. Other systems HPO4–2  H2PO4– system
Proteins are capable of binding H+
Hemoglobin
M. Zaharna Clin. Chem. 2015

11. Regulation of Acid-Base Balance: Lungs and Kidneys
The lungs and kidneys play important roles in regulating blood pH.
The lungs regulate pH through retention or elimination of CO2
by changing the rate and volume of ventilation.
The kidneys regulate pH by:
excreting acid, primarily in the ammonium ion,
and by reclaiming HCO3- from the glomerular filtrate.
M. Zaharna Clin. Chem. 2015

12. Regulation of Acid-Base Balance by Lungs
End product of aerobic metabolic process is CO2
diffuses out the tissue into plasma and RBC
In Plasma & RBCs:
a small amount of CO2 is dissolved
or combined with proteins to form carbamino compounds.
Most of the CO2 combines with H2O to form H2CO3, which quickly dissociates into H+ and HCO3-
M. Zaharna Clin. Chem. 2015

13. M. Zaharna Clin. Chem. 2015

14. Regulation of Acid-Base Balance by Lungs
The dissociation of H2CO3 causes the HCO3- concentration to increase in the RBCs and diffuse into the plasma.
To maintain electroneutrality chloride diffuses into the cell (chloride shift)
M. Zaharna Clin. Chem. 2015

15. Regulation of Acid-Base Balance by Lungs
In the lungs:
The process is reversed.
Inspired O2 diffuses from the alveoli into the blood and is bound to hemoglobin, forming oxyhemoglobin (O2Hb).
The H+ that was carried on the (reduced) hemoglobin in the venous blood is released to recombine with HCO3- to form H2CO3,
which dissociates into H2O and CO2.
M. Zaharna Clin. Chem. 2015

16. Regulation of Acid-Base Balance by Lungs
The CO2 diffuses into the alveoli and is eliminated through ventilation.
The net effect of the interaction of these two buffering systems is a minimal change in H+ concentration between the venous and arterial circulation.
M. Zaharna Clin. Chem. 2015

17. Interrelationship of the bicarbonate and hemoglobin buffering systems
M. Zaharna Clin. Chem. 2015

18. Regulation of Acid-Base Balance by Lungs
When the lungs do not remove CO2 at the rate of its production (hypovent.) it accumulates in the blood,
causing an increase in H+ concentration.
If, however, CO2 removal is faster than production (hypervent,)
the H+ concentration will be decreased.
Consequently, ventilation affects the pH of the blood.
M. Zaharna Clin. Chem. 2015

19. Regulation of Acid-Base Balance by Lungs
A change in the H+ concentration of blood that results from nonrespiratory disturbances causes the respiratory center to respond
altering the rate of ventilation in an effort to restore the blood pH to normal.
The lungs, by responding within seconds, together with the buffer systems, provide the first line of defense to changes in acid-base status.
M. Zaharna Clin. Chem. 2015

20. Kidney system Main role is reabsorption of bicarbonate
Kidneys respond to increase or decrease in hydrogen ions by selectively excreting or reabsorbing:
Hydrogen ions
Sodium
Chloride
Phosphate
Ammonia
Bicarbonate
M. Zaharna Clin. Chem. 2015

21. Reabsorption of Bicarbonate
Reabsorption of bicarbonate (HCO3 –) takes place in the renal tubule cells.
Na + is exchanged for H+ ion.
H+ ion combines with the HCO3 – and carbonic acid dissociates into H2O and CO2.
CO2 diffuses into the tubule cells combining with H2O forming H2CO3.
Reabsorption of bicarbonate in the blood system.
Urinary H+ combines with HPO4– and NH3.
M. Zaharna Clin. Chem. 2015

22. carbonic anhydrase
M. Zaharna Clin. Chem. 2015

23. Acid-Base Disorders Acidosis (decrease pH) → acidemia
Alkalosis (increased pH) → alkalemia
metabolic or respiratory
A disorder caused by ventilatory dysfunction is termed primary respiratory acidosis or alkalosis.
A disorder resulting from a change in the bicarbonate level is termed a nonrespiratory disorder.
Technically, the suffix -osis refers to a process in the body; the suffix -emia refers to the corresponding state in blood
M. Zaharna Clin. Chem. 2015

24. Acid-Base Disorders
Body's cellular and metabolic activities are pH dependent
The body tries to restore acid-base homeostasis whenever an imbalance occurs.
This action is termed compensation
Done by altering the factor not primarily affected by the pathologic process.
eg., if the imbalance is of nonrespiratory origin, the body compensates by altering ventilation.
For disturbances of the respiratory component, the kidneys compensate by selectively excreting or reabsorbing anions and cations.
M. Zaharna Clin. Chem. 2015

25. Acid-Base Disorders Lungs can compensate immediately but:
the response is short term
and often incomplete.
The kidneys compensate are slower to respond (2-4 days) but:
the response is long term
and potentially complete
M. Zaharna Clin. Chem. 2015

26. Metabolic (non-respiratory) Acidosis
Decrease pH, increase H+
Bicarbonate decreased (<24 mmol/L)
Caused by:
acid producing substance or process
or reduce excretion of acids
Compensation:
1o - Respiratory compensation:
Hyperventilation, decrease CO2 in circulation.
2o - Renal compensation:
increase H ion loss by increasing H2PO4 and NH4 excretion and retain HCO3-
acid-producing substance, such as ammonium chloride or calcium chloride, or by excessive formation of organic acids as seen with diabetic ketoacidosis and starvation
M. Zaharna Clin. Chem. 2015

27. Respiratory Acidosis Compensation Caused by hypoventilation
decrease the elimination of CO2 in the lungs, it builds up in the blood
decrease in pH, increase in H and HCO3
Diseases: emphysema, drugs , congestive heart failure, bronchopneumonia.
Compensation
Renal compensation
increase H+ excretion & increase reabsorption of HCO3-
Emphysema gradually damages the air sacs (alveoli) in the lungs, making progressively more short of breath
M. Zaharna Clin. Chem. 2015

28. Metabolic (non-respiratory ) alkalosis
HCO3- increased, H+ decreased, pH increased
Causes of nonrespiratory alkalosis:
excess administration of NaHCO3
ingestion of HCO3– producing salts such as Na- lactate, citrate or acetate
excessive loss of acid through vomiting
Compensation
Respiratory compensation
Hypoventilation with CO2 retention
Renal compensation
excrete HCO3- and retain H+ ions.
M. Zaharna Clin. Chem. 2015

29. Respiratory alkalosis
Decreased CO2, decreased H+, increased pH
Causes of respiratory alkalosis include:
hypoxemia;
chemical stimulation of the respiratory center by drugs, such as salicylates;
pulmonary fibrosis.
Compensation
Renal compensation
decrease renal excretion of H+ ions, HCO3- excreted.
M. Zaharna Clin. Chem. 2015