patholophysiology of acid base disturbance Pathophysiology（病理生理学） Pathology uploaded by prabesh 杰诗

1. Dept. of PathologyDept. of Pathology
Medical CollegeMedical College
Hunan Normal UniversityHunan Normal University
(( 湖南 范大学医学院病理学教研室师湖南 范大学医学院病理学教研室师 )) 1
Chapter 3Chapter 3
Acid-Base Balance andAcid-Base Balance and
ImbalanceImbalance
（酸 平衡紊乱）碱（酸 平衡紊乱）碱

2. 22
Acid-Base Balance and ImbalanceAcid-Base Balance and Imbalance
a.a. Acid-base homeostasisAcid-base homeostasis
b.b. Parameters of acid-baseParameters of acid-base
balancebalance
c.c. Simple acid-base disturbanceSimple acid-base disturbance
 Metabolic acidosisMetabolic acidosis
 Respiratory acidosisRespiratory acidosis
 Metabolic alkalosisMetabolic alkalosis
 Respiratory alkalosisRespiratory alkalosis

3. The process which is regulated automatically
by the body to keep relatively stable between
acidity and basicity.
Q: Why balanced pH?
Normal pH range: 7.35 ~ 7.45
Section 1
Acid-base Homeostasis

4. Concepts of Acid and Base
§2. Base: an acceptor of H+
.
§1. Acid: a donor of hydrogen ions
( H+
).

5. AcidsAcids
 Volatile acid ( 挥发
酸 )
 Fixed acid ( 固定酸 )

6. An acid excreted through the lungs
as a gas.
Volatile Acid
Sources of CO2:
Metabolism of biomolecules
CO2CO2 ＋ H2OH2O H2CO3
(300-400 L/d)
H+ HCO3
-＋

7. Fixed (non-volatile) AcidFixed (non-volatile) Acid
Acid produced in the body from sources other
than CO2.
Excreted by the kidneys.
Sources: From proteins:
sulfate, phosphate, urate
From carbohydrates:
Lactate, pyruvate, glycerate
From lipids:
Adenylate, pyrophosphate

8. Bases
(Alkali)Sources
Amino acid metabolism (NH3)
Fruits and vegetables
Citric acid, maleic acid, oxalic acid…
Why bases produced from acids?
Fruits → CO2, H2O and ions (e.g., Na+
)
Bases << Acids
Acids: Fixed << Volatile

9. 2. Regulation of Acid-Base Balance2. Regulation of Acid-Base Balance
 Buffer Systems
Blood
Cells
Bone
 Lungs
 Kidneys
Three Levels

10. Buffer acid Buffer base
Buffer systems in the bloodBuffer systems in the blood
Ability
53
5
7
35

11. Bicarbonate/Carbonic AcidBicarbonate/Carbonic Acid
Buffer SystemBuffer System
HCO3
-
/H2CO3
The ratio of HCO3
-
vs H2CO3
determines the blood pH.
HCl + HCO3
-
→ Cl-
+ H2CO3 → CO2 + H2O
NaOH + H2CO3 → NaHCO3 + H2O
Open buffer system
Lungs
Kidneys

12. HbHb--
/HHb/HHb 、、 HbOHbO22
--
/HHbO/HHbO
22
Hemoglobin Buffer System
Only in RBC
Regulates volatile acid

13. [H ＋
] H ＋
+Pr-
→HPr
[K ＋
] K
＋
Cl-
Cl-
HCO3
-
HCO3
-
Mechanism of Buffering in the CellsMechanism of Buffering in the Cells

14. Regulation of Acid-BaseRegulation of Acid-Base
Balance by the LungsBalance by the Lungs
Regulation of Volatile AcidRegulation of Volatile Acid
++HH22COCO33 HH22OO COCO22 RespirationRespiration
HH++
↑↑
++
HCOHCO33
--

15. Regulation by the Kidneys
 Excrete fixed acids
H+
-Na+
(NH4
+
-Na+
) exchange to excrete H+
(or NH4
+
)
Retaining Na+
 Maintain plasma [HCO3
-
]
Na+
-HCO3
-
co-transported into capillaries

16. Na+
Excretion of H+
and Reabsorption of HCO3
-
at the proximal tubule
Capillary Epithelial Cell Tubule
H2O + CO2
H+
Na+
H2CO3
HCO3
-
H+
CA
CA: Carbonic anhydrase

17. H2O + CO2
H+
H2CO3
HCO3
-
H+
Glutamine
NH3 NH4
+
+
NH3
NH3
Na+
NH4
+
+
Na+
Excretion of NH4
+
CA
Capillary Epithelial Cell Tubule

18. Cells
Volatile
acid (H2CO3)
Fixed
acids
Lungs KidneysPlasma
Production and Regulation of Acids and Bases
Food
Digestion
Absorption
Metabolism

19. Characteristics of Acid-Base Regulations
①Buffer systems in the blood ：
Fast;
Buffer effect can not be sustained.
②Buffer in the cells ：
Very strong and fast (3 － 4 h);
Electrolytes imbalance (hyperkalemia) may occur.
③Respiratory Regulation ：
Strong and very fast (peak in 30 min);
Eliminate volatile acid (CO2
) [and fixed acids].
④Renal Regulation ：
Strong in eliminating fixed acids and retaining HCO3
-
;
Slow (3-5 days).

20. 2727
Acid-Base Balance and ImbalanceAcid-Base Balance and Imbalance
a.a. Acid-base homeostasisAcid-base homeostasis
b.b. Parameters of acid-baseParameters of acid-base
balancebalance
c.c. Simple acid-base disturbanceSimple acid-base disturbance
 Metabolic acidosisMetabolic acidosis
 Respiratory acidosisRespiratory acidosis
 Metabolic alkalosisMetabolic alkalosis
 Respiratory alkalosisRespiratory alkalosis

21. Section 2
Parameters of Acid-Base Balance
(Blood Gas Analysis)
1. pH
2. PaCO2
3. SB
4. AB
5. BB
6. BE
7. AG

22. 1. pH
pH < 7.35: Acidosis
pH > 7.45: Alkalosis
§2. Normal value ：
7.35 ～ 7.45 (average ： 7.40)

23. Henderson-Hasselbalch EquationHenderson-Hasselbalch Equation
pH = pKa + LogpH = pKa + Log
[HCO[HCO33
－－
]]
[H[H22COCO33]]
= pKa + Log= pKa + Log 2424
1.21.2
= 6.1 + 1.3 = 7.4

24. 2. PaCO2
Partial pressure of carbon dioxide (CO2) in
plasma (artery)
Significance: respiratory parameter
Normal Value: 33~46 mmHg (Average:
40 ）PaCO2 ↑:
Respiratory Acidosis
Metabolic Alkalosis after compensation
PaCO2 ↓:
Respiratory Alkalosis
Metabolic Acidosis after compensation

25. Normal Value: 22 ～ 27 mmol/L (Average: 24)
[HCO3
-
] measured under “standard condition”
 37~38°C
 Hb fully oxygenated
 PaCO2 @ 40 mmHg
 37~38°C
 Hb fully oxygenated
 PaCO2 @ 40 mmHg
3. Standard Bicarbonate, SB
SB ↑: Metabolic Alkalosis
SB ↓: Metabolic Acidosis
Not affected by respiration.
Only reflecting metabolic factor.

26. Actual Bicarbonate, ABActual Bicarbonate, AB
Reflecting:
Both metabolic and respiratory factors
HCO3
-
measured under “actual condition”.
Sealed off from air
PaCO2 and O2 at original level
Sealed off from air
PaCO2 and O2 at original level
Normal Value: the same as SB (24 mmol/L)

27. AB > SB, PaCO2
↑
Respiratory acidosis
(metabolic alkalosis after compensation)
AB < SB, PaCO2
↓
Respiratory alkalosis
(metabolic acidosis after compensation)
In physiological situation: AB = SB
In pathological situation: AB ≠ SB
AB vs. SB

28. 4.4. Buffer Base, BBBuffer Base, BB
Meaning:
BB ↑ － Metabolic alkalosis
BB ↓ － Metabolic acidosis
Normal: 45 ～ 52 mmol/L (Average:
48 )
The sum of all alkaline buffer substances in plasma
(HCO3
-
, HPO4
2-
, Pr-
, Hb-
, HbO2
-
)

29. 5. Base Excess, BE
The amount of a fixed acid or base that must be
added to a blood sample to achieve a pH of 7.4 under
standard condition.
Normal value: -3.0 - +3.0
pH 7.35 7.4 7.45
BE -3.0 0 +3.0
Metabolic acidosis Normal Metabolic alkalosis
§3. Meaning:

30. 6.6. Anion GapAnion Gap ，， AGAG
The difference between
undetermined anion (UA) and
undetermined cation (UC) in
the plasma (AG = UA - UC).
AG↑ (AG>16): ↑ Fixed acids
(metabolic acidosis)
AG↓: little clinic meaning
Undetermined
AG = Na+
- (Cl-
+ HCO-
3)
= 140 - (104 + 24)
= 12 mmol/L (10 ~ 14 mmol/L)

31. 3838
Acid-Base Balance and ImbalanceAcid-Base Balance and Imbalance
a.a. Acid-base homeostasisAcid-base homeostasis
b.b. Parameters of acid-baseParameters of acid-base
balancebalance
c.c. Simple acid-base disturbanceSimple acid-base disturbance
 Metabolic acidosisMetabolic acidosis
 Respiratory acidosisRespiratory acidosis
 Metabolic alkalosisMetabolic alkalosis
 Respiratory alkalosisRespiratory alkalosis

32. pH
Acidosis
Respiratory
[HCO3
-
]↓ H2CO3↑
Metabolic
Alkalosis
[HCO3
-
]↑ H2CO3 ↓
Metabolic Respiratory
Types of Acid-Base DisturbanceTypes of Acid-Base Disturbance

33. 4040
Acid-Base Balance and ImbalanceAcid-Base Balance and Imbalance
a.a. Acid-base homeostasisAcid-base homeostasis
b.b. Parameters of acid-baseParameters of acid-base
balancebalance
c.c. Simple acid-base disturbanceSimple acid-base disturbance
 Metabolic acidosisMetabolic acidosis
 Respiratory acidosisRespiratory acidosis
 Metabolic alkalosisMetabolic alkalosis
 Respiratory alkalosisRespiratory alkalosis

34. §2. Causes ： Acids too much
Bases too little
Metabolic acidosis is defined as a
decrease of pH induced by primary decrease
in plasma HCO3
-
concentration.
§1. Concept ：
Metabolic acidosis

35. ① Production of fixed acids ↑ ：
Lactic acidosis (↑ glycolysis)
Ketoacidosis (↑ lipolysis)
③ Excessive intake of acids ：
Aspirin (acetylsalicylic acid) poisoning
Excessive intake of NH4Cl, etc.
1) Acids too much (consuming HCO3
-
)
② Elimination of acids↓ ：
Renal failure (↓GFR)
Renal Tubule Acidosis (RTA):
excretion of H+
↓ in the collecting tubule.
④ Hyperkalemia ：
↑ H+
-K+
exchange
Metabolic acidosis

36. ① HCO3
-
loss ↑ ：
Loss from intestinal juice
(diarrhea)
③ HCO3
-
dilution ：
massive infusion of glucose or NS in a short time.
② HCO3
-
reabsorption ↓ ：
2) Bases too little
Renal Tubular Acidosis (RTA)
Metabolic acidosis

37. §3. Classification ：
2) High AG metabolic acidosis ：
primary HCO3-↓
AG↑ due to any kind of fixed acids
except Cl-
(Normochloremic MAc)
e.g., shock, renal failure
1) Normal AG metabolic acidosis ：
primary HCO3
-
↓
compensatory ↑ of Cl-
(Hyperchloremic MAc)
HCO3
-
losing ↑ : diarrhea, intestinal fistulas;
HCO3
-
reabsorption ↓ : RTAⅡ
Normal Normal AG MAc High AG MAc
Metabolic acidosis

38. §4. Compensation ：
Acid
extracellular fluid
cell
Pulmonary regulation is a main way in metabolic acidosis.
Metabolic acidosis

39. Example
1. 1 diabetes patient ：
pH 7.32, HCO3
-
15 mmol/L, PaCO2
30 mmHg ；
predict PaCO2
= 1.5×15 + 8±2 = 30.5±2 = 28.5 ～ 32.5
measured PaCO2
= 30, within 28.5 ～ 32.5;
Therefore, simple MAc
Equation ： predict PaCO2
= 1.5×[HCO3
-
] ＋ 8±2
Judgement ：
If measured PaCO2
within predicted PaCO2 , simple MAc
If measured > predicted maximum, CO2
retention, MAc + RAc
If measured < predicted minimum, CO2
too less, MAc + RAl
Metabolic acidosis

40. 1.2 shock patient with pneumonia:
pH 7.26 ， HCO3
-
16 mmol/L ， PaCO2
37 mmHg ；
predicted PaCO2
= 1.5×16 + 8±2 = 32±2 = 30 ～ 34
measured PaCO2
=37, exceed predict maximum 34;
Therefore, MAc + RAc
Metabolic acidosis

41. pH ↓
PaCO2
↓
HCO3
-
↓↓
AB ↓
SB ↓
BB ↓
BE ↓ (negative value increased)
(in the case of simple MAc)
§5. Changes of blood gas parameters :
Metabolic acidosis

42. §6. Effects on organism
1) Cardiovascular system
① Cardiac arrhythmias ：
in connection with hyperkalemia
K +
H+
Metabolic acidosis

43. ② Negative inotropic (contractive) action
：
inhibit the binding of Ca2+
with troponin
inhibit the influx of Ca2+
from
extracellular space
inhibit the release of Ca2+
into cytoplasm
from endoplasmic reticulum.
H+
↑ directly
impairs
myocardial
contraction
↓③ Response of vascular smooth
muscle to catecholamine (CA).
Metabolic acidosis

44. 2) Central nervous system ：
The main manifestations are inhibitory: lethargy,
disorientation, unconsciousness, or coma.
Mechanism:
4) Respiratory system:
deep and rapid respiration ( Kussmaul’s breathing).
3) Osseous system: calcium phosphate in bone buffers
chronic metabolic acidosis → rickets and osteodystrophy
(in chronic renal failure).
GABA ↑ (Gamma-aminobutyric Acid) (inhibitory
neurotransmitter)
Glutamate decarboxylase
↓pH
Glu
GABA
Metabolic acidosis

45. 5) Urinary system
Urine is usually acidic in MAc.
But: paradoxical alkaline urine
(hyperkalemia)
K +
H+
DistalTubule
Metabolic acidosis

46. §7. Principles of prevention and treatment ：
１ ) Correction of underlying disorders.
２ ) Administration of NaHCO3 ：
1.5% NaHCO3
or 1/6 M sodium lactate
★ After the correction of acidosis, attention should be paid
to prevent hypokalemia and convulsion ( 抽搐 ) (induced by
decreased free Ca2+
(hypocalcemia)).
3) Correction of water-electrolyte disturbances :
Metabolic acidosis

47. Hypocalcemia convulsion
Ca2+
+ plasma proteins bound calcium
OH-
H+
Metabolic acidosis