1. Acid-base Balance (ABB)
Vladimíra Kvasnicová

2. Definition - REPETITIONpH
acid
base
dissociation constant
buffers

3. The figure was found at http://www. colorado
The figure was found at (April 2007)

4. the border between strong and weak acid
= nedisociovaná kyselina
= volný H+
= volný anion
The figure was found at (April 2007)

5. + 3 HCl
The figure was found at (April 2007)

6. [CO2] =  x pCO2  = 0,226 for pCO2 expressed in kPa
 = 0,03 for pCO2 expressed in mmHg

7. Dissociation constant and buffer pH
! the best buffering properties: pH = pK ± 1 !
pH = pK + log (1 / 1)  pH = pK
pH = pK + log (10 / 1)  pH = pK + 1
pH = pK + log (1 / 10)  pH = pK - 1

8. Calculate the ratio of components of the phosphate buffer (HPO42- / H2PO4-) pK2 = 7,0if
a) pH = 7,4 (blood)
b) pH = 7,0 (cell)
c) pH = 6,0 (urine)

9. The source and fate of acids / bases
source of acids: metabolism
source of bases: food
fate:
transformation by the metabolism
excretion

10. ~ mmol / den
The figure has been adopted from J.Koolman, K.H.Röhm / Color Atlas of Biochemistry, 2nd edition, Thieme 2005

11. The metabolism produces acids:
carbon skeleton → CO2+H2O → HCO3-+ H+
saccharides → glucose → pyruvate, lactate + H+
triacylglycerols → fatty acids, ketone bodies + H+
phospholipids → phosphate + H+
proteins → amino acids → sulfate, urea + H+

12. Acids formed in the human body
metabolic (nonvolatile) acids → excretion by the kidneys
glucose → lactic acid  lactate + H+
fatty acids → ketone bodies: acetoacetic acid  acetoacetate + H+
-hydroxybutyric acid  -hydroxybutyrate + H+
amino acids Cys and Met → H2SO4 → sulfate + 2H+
phospholipids → H3PO4  HPO H+
respiratory (volatile) acid → excretion by the lungs
CO2 + H2O  H2CO3  HCO3- + H+

13. The order of systems which participate in ABB
buffers (changes of pH caused by common metabolism)
the lungs (CO2)
the kidneys (H+, HCO3-)
blood pH can be also affected by the liver (synthesis of urea, metabolism of lactate) and the heart (oxidation of ketone bodies and lactate)

14. The liver – detoxication of ammonia according to the ABB state
amino acids
LIVER, MUSCLE
carbon skeleton
LIVER
urine
urine
favourized during alkalemia
favourized during acidemia
The figure has been adopted from: Klinická biochemie. Požadování a hodnocení biochemických vyšetření. Karolinum, Praha, ISBN 80‑7184‑649‑3

15. GLUTAMINE cycle in the liver
The figure has been adopted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley‑Liss, Inc., New York, ISBN 0‑471‑15451‑2

16. Principal buffer systems
fluid
buffer
note
ISF
bicarbonate
buffers metabolic acids
phosphate
low concentration
proteins
blood
hemoglobin
buffers CO2 (H2CO3)
plasma proteins
ICF
important buffer
urine
related to almost all titratable acidity of the urine
ammonium
important: excretion of both NH3 and H+; cation!!!

17. Blood buffers - overview
bicarbonate buffer: HCO3-/CO2
pK(H2CO3) = 6, mM
phosphate buffer: HPO42-/H2PO4-
pK(H2PO4-) ≈ 7, mM
hemoglobin: Hb-/Hb-H+
pK(HHbO2) = 6,17 pK(HHb) = 7, g/L
proteins: protein/protein-H g/L
pK = 4 – 12 (mainly Asp, Glu and His)

18. Blood buffers pufr plasma erythrocytes sum HCO3-/CO2 35 % 18 % 53 %
Hb/Hb-H+ -
plasma proteins
7 %
inorganic phosphate
1 %
2 %
organic phosphate
3 %
43 %
57 %
100 %

19. Excretion of CO2 by the lungs
(March 07)

20. Excretion of H+ by the kidneys (I)
(April 2007)

21. Excretion of H+ by the kidneys (II)
(April 2007)

22. Excretion of H+ by the kidneys (III)
(April 2007)

23. Urine buffers 1 excreted H+  1 reabsorbed HCO3-
NH3 + H+ → NH4+ (50 mmol H+/day)
H+ + HPO42- → H2PO4- (20 mmol H+/day)

24. ABB disorders
The figure has been adopted from J.Koolman, K.H.Röhm / Color Atlas of Biochemistry, 2nd edition, Thieme 2005

25. CO2 produced by metabolic reactions HCO3- regenerated in the kidneys
HCO3- lost by buffering endogenously produced acids
CO2 excreted by the lungs
(April 2007)

26. Primary disorders of ABB
Resp.
Mtb.
pCO2
HCO3-
(April 2007)

27. http://romerosnap1.phol.cwru.edu/AcidBase-SOMy1.htm (April 2007)
24 mM
(April 2007)

28. = effort to readjust plasma pH back toward normal
Compensation
= effort to readjust plasma pH back toward normal
one system compensates disfunction of the other system
respiratory disorders are compensated by the kidneys (3-5 days)
metabolic disorders are compensated by the lungs (12-24 hours) or corrected by the kidneys

29. EXAMPLE OF COMPENSATION:
metabolic alkalosis
uncompensated compensated
(April 2007)

30. Physiological values of ABB (Astrup)
pO2 8, ,7 kPa
pCO2 4,80 - 5,90 kPa
HCO ± 2 mM
BE 0 ± 2,5 mM

31. Respiratory Acidosis (RAc)
cause: hypoventilation
  CO2 + H2O  H2CO3  HCO3- + H+
buffering: H+ + Hb  Hb-H+  loss of base
result: * increase of pCO2  decrease of pH
* increase of HCO3- and decrease of other buffer bases, especially of Hb  BE = 0
when pO2   lactate  (+ MAc)
compenstaion:
 resorption of HCO3- in the kidneys  acidic urine
 positive BE

32. Respiratory Alkalosis (RAl)
cause: hyperventilation
  CO2+ H2O  H2CO3 HCO3- + H+
buffering: Hb-H+  Hb + H+  increase of bases
reult:
* decrease of pCO2  increase of pH
* decrease of HCO3- and increase of other buffer bases  BE = 0
compensation:
increased excretion of HCO3- by the kidneys
 negative BE

33. Respiratory disorders
deviation from equilibrium to other isobars
A (C) = primary imbalance
B (D) = compensated
The figure has been adopted from: Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley‑Liss, Inc., New York, ISBN 0‑471‑15451‑2

34. Metabolic Acidosis (MAc)
causes: 1) overproduction of acids (H+) in mtb
   increased anion gap
2) increased excretion of HCO3-
 normal anion gap
ad1) metabolism produces excess of acids   H+
buffering: H+ + HCO3-  H2CO3  H2O + CO2
 excretion of CO2: hyperventiltion (= compensation)
H+ are also buffered by bases of nonbicarbonate buffers
 decrease of BE (HCO3- and other buffer bases)
ad2) loss of HCO3- e.g. diarrhoea, inhibitors of CA

35. Metabolic Acidosis (II)
result:
* decrease of pH
* negative BE
* acidic urine ( phosphates and NH4+),  decreased excretion HCO3-
* deep breathing
(stimulation of the respiratory centre by high concentration of H+)
 later:  pCO2 (= compensation)
compensation:
hyperventilation  other decrease of HCO3-

36. Metabolic Alkalosis (MAl)
cause: 1) increased excretion of protons
(e.g. vomitting,  resorption of NaHCO3)
2) increased ingestion of bases
buffering:
 H+  CO2 + H2O  H2CO3  HCO3- + H+
other buffers  H+
  HCO3- and other buffer bases  positive BE
result: * increase of pH
* positive BE
*  K+ in blood  heart beat imbalance
compensation: hypoventilation

37. deviation from equilibrium proceeds at the same isobar
Metabolic disorders
deviation from equilibrium proceeds at the same isobar
E (G) = primary imbalance
F (H) = compensated
The figure has been adopted from: Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley‑Liss, Inc., New York, ISBN 0‑471‑15451‑2

38. Kalemia (= concentration of K+ in blood)
3,8-5,3 mM
acidosis  release of K+ from cells  hyperkalemia  loss of K+ with urine (quick alkalization of the organism by treatment can cause consequent hypokalemia  danger of heart beat imbalance)
alkalosis  K+ replaces H+ in cells  decrease of K+ in blood  hypokalemia; K+ is excreated into urine instead of H+ (exchange with Na+)

39. Case 1
A 70 year old man suffering from chronic lung disease, was admitted with an acute exacerbation. After admission testing (A), vigorous physiotherapy and medical treament were instituted, but his condition deteriorated (B). Artificial ventilation was started. 6 hours later results were (C). After 12 hours he had a seizure (D).  
A B C D
pH 7,30 7,24 7,40 7,54
pCO2 (kPa) 9, , ,73 5,73
HCO3- (mM)

40. Case 2
A young woman was admitted unconscious, following a head injury. X-Ray showed a skull fracture and CT showed extensive cerebral contusions. There was no change over three days.  
A B
pH 7,52 7,48
pCO2 (kPa) 3,47 3,87
HCO3- (mM)

41. Case 3
A patient with vague symptoms, fever and hyperventilation presented in the Emergency Room:
Na mM
K+ 3,5 mM
Cl mM
HCO mM
pH 7,39
pCO2 2,67 kPa

42. Case 4
 A 45 year old man was admitted with a history of persistent vomiting. He had a long history of dyspepsia which had gone untreated except with proprietary remedies.
Examination revealed dehydration and shallow respirations.  
pH 7,56
pCO2 (kPa) 7,20
HCO3- (mM) 45
K+ (mM) 2,8

43. Case 5
A 23 year old mechanic was brought to ER 12 hours after drinking antifreeze. He was agitated and confused. His sclerae were icteric.
Na+ (mM) 137
K+ (mM) 5,4
Cl- (mM) 95
HCO3- (mM) 4
glukóza (mM) 2,5
pH 6,95
pCO2 (kPa) 2,0