1. Acid-Base Disturbance
Department of Pathophysiology
Shanghai Jiao-Tong University School of Medicine

2. main topics
Acid Base Physiology
Acid Base disturbances

3. Acid Base disturbances
Concept of Acid Base disturbance
Acid Base parameter/Arterial Blood Gases (ABGs)
Clinical Acid Base disorders
Pathogenesis of Acid Base disorders
Influence of Acid Base disorders
Mixed Acid/Base disorders

4. The concept of Acid Base balance

5. Acid Base balance
Acid-base balance refers to the mechanisms the body uses to keep its fluids close to neutral pH (that is, neither basic nor acidic) so that the body can function normally.
Arterial blood pH is normally closely regulated to between 7.35 and 7.45.

6. acids？
bases？
Any ionic or molecular substance that can act as a proton donor.
Strong acid：HCl, H2SO4, H3PO4.
Weak acid：H2CO3, CH3COOH.
Any ionic or molecular substance that can act as a proton acceptor.
Strong alkali：NaOH, KOH.
Weak alkali：NaHCO3, NH3, CH3COONa.

7. Intracellular metabolism
Origin of acids
Much more
Intracellular metabolism
Volatile acids
CO2+H2O=H2CO3
300~400L CO2 (15mol H+)
Lactic acid
Ketone bodies
Sulfuric acid
Phosphoric acid
50~100 mmol H+
Fixed acids
Origin of bases
less
NH3 , sodium citrate, sodium lactate

8. Acid Base balance & regulation

9. pH
- pH of ECF is between 7.35 and Deviations, outside this range affect membrane function, alter protein function, etc.
- You cannot survive with a pH <6.8 or >7.7
Acidosis- below 7.35
Alkalosis- above 7.45
CNS function deteriorates, coma, cardiac
irregularities, heart failure, peripheral
vasodilation, drop in Bp.

10. Given that normal body pH is slightly alkaline and that normal metabolism produces acidic waste products such as carbonic acid (carbon dioxide reacted with water) and lactic acid, body pH is constantly threatened with shifts toward acidity.
In normal individuals, pH is controlled by two major and related processes; pH regulation and pH compensation. Regulation is a function of the buffer systems of the body in combination with the respiratory and renal systems, whereas compensation requires further intervention of the respiratory and/or renal systems to restore normalcy.

11. In chronic metabolic acidosis
H＋ load
ECF
lung
ICF
Renal
Bone
Buffers
RBC
Respiratorycontrol
H+ excretion
bicarbonate reabsorption
Release bone salt
H＋－K＋
exchange Hb
buffers
others
Ca2＋＋H2PO4
In chronic metabolic acidosis
H2CO3 CO2
Acid excretion
Expiration
Immediately
minutes
hours
days
Very slow

12. Buffering system ECF Plasma NaHCO3/ H2CO3 NaPr/HPr* Na2HPO4/NaH2PO4
intercellular NaHCO3/ H2CO Na2HPO4/NaH2PO4
fluid
ICF** KPr/HPr K2HPO4/KH2PO KHCO3 /H2CO3
organic acids
RBC KHb/HHb KHbO2/HHbO K2HPO4/KH2PO4
KHCO3/ H2CO3
* HPr：protein； ** muscle cells。

13. buffering？ HA H+ + A Ka = [ H+ ]  [ A ] [ HA ] [ H+ ] = Ka  [ HA ]
pH =
pKa + lg
[ HA ]
[ A ]

15. Henderson-Hasselbalch equation：
pH  pKa ＋ log（ HCO3－ / H2CO3）
pH  pKa ＋ log（ HCO3－ / ·PaCO2）
pH  6.1 ＋ log（ 24 /0.226·5.32）
pH  6.1 ＋ log（ 24 / 1.2）
pH  6.1 ＋ 1.3
pH  7.4
（: the factor which relates PCO2 to the amount of CO2 dissolved in plasma）

16. The compensation effect of RBC
Primary changing
CO2
CO2 + H2O CA
H2CO3
RBC
plasma CA
HCO3
HCO3 H+
C l
C l
Hb buffering
Cl¯ transfer
CA ：carbonic anhydrase
The compensation effect of RBC

17. Bicarbonate
Reabsorption
Na+-H+ exchange of proximal tubule.
H+ secretion in collecting tubule is mediated by H+ ATPase pump in luminal membrane and a Cl-HCO3- exchanger in basolateral membrane. The H+ ATPase pump is influenced by aldosterone, which stimulates increased H+ secretion.
Hydrogen ion secretion in the collecting tubule is the process primarily responsible for acidification of the urine, particularly during states of acidosis. The urine pH may fall as low as 4.0.

18. Excretion of titratable acids is dependent on the quantity of phosphate filtered and excreted by the kidneys, which is dependent on one's diet, and also PTH levels. As such, the excretion of titratable acids is not regulated by acid base balance and cannot be easily increased to excrete the daily acid load.

19. Ammoniagenesis  NH4+ excretion
The major adaptation to an increased acid load is increased ammonium production and excretion. Because the rate of NH4+  production and excretion can be regulated in response to the acid base requirements of the body.
●The process of ammoniagenesis occurs within proximal tubular cells.
●The generation of new HCO3¯ ions is probably the most important feature of this process.

20. Summary uBuffers only provide a temporary solution.
uKidney: are the ultimate H+ ions balance. Slow acting mechanisms can eliminate any imbalance in H+ levels.
uLung: responds rapidly to altered plasma H+ concentrations, and keep blood levels under control until the kidneys eliminate the imbalance.

22. Acid base disturbance

23. Definition of acid-base disorders或
An acid base disorder is a change in the normal value of extracellular pH that may result when renal or respiratory function is abnormal or when an acid or base load overwhelms excretory capacity.

24. Simple Acid-Base Disorders
Clinical disturbances of acid base metabolism classically are defined in terms of the HCO3¯  /CO2  buffer system.
Acidosis – process that increases [H+] by increasing PCO2 or by reducing [HCO3-] Alkalosis – process that reduces [H+] by reducing PCO2 or by increasing [HCO3-]
Henderson Hasselbalch equation: 
pH = log [HCO3-]/ 0.03 PCO2
Since PCO2 is regulated by respiration, abnormalities that primarily alter the PCO2 are referred to as respiratory acidosis (high PCO2) and respiratory alkalosis (low PCO2).
In contrast, [HCO3¯] is regulated primarily by renal processes. Abnormalities that primarily alter the [HCO3¯] are referred to as metabolic acidosis (low [HCO3¯]) and metabolic alkalosis (high [HCO3¯]).

26. Acid Base parameter /Arterial Blood Gases (ABGs)

27. Arterial Blood Gas Sampling

28. pH
pH is a measurement of the acidity of the blood, reflecting the number of hydrogen ions present.
pH = - log [H+]
pH7.45：alkalosis
pH7.35：acidosis
pH ：
①Acid-base balance.
②Acidosis or alkalosis with complete compensation.
③A mixed acidosis and alkalosis, both events have opposite effects on pH, may also have a normal pH.

29. PaCO2 (Partial Pressure of Carbon Dioxide)
The amount of carbon dioxide dissolved in arterial blood.
Normal: 4.39 ～ 6.25kPa（33 ～ 46 mmHg）
Average: 5.32 kPa（40 mmHg）
Respiratory acidosis: > 46 mmHg (> 6 .25kPa)
Respiratory alkalosis: <33 mmHg (< 4.39 kPa)
The PaCO2 reflects the exchange of this gas through the lungs to the outside, so it is called “respiratory parameter”.

30. SB, AB
These two parameters are designed for HCO3¯ concentration in plasma.
SB is measured under “standard condition”, AB is measured under “actual condition”. The difference between two cases is that the former rules out the respiratory effect on HCO3¯ concentration measurement, but the later does not.
HCO3¯
Normal: 22～27mmol/L
Metabolic acidosis: <22 mmol/L
Metabolic alkalosis: > 27 mmol/L
[Standard Bicarbonate: Calculated value. Similar to the base excess. It is defined as the calculated bicarbonate concentration of the sample corrected to a PCO2 of 5.3kPa (40mmHg).

31. BE (base excess)
The base excess indicates the amount of excess or insufficient level of bicarbonate in the system. (A negative base excess indicates a base deficit in the blood.) A negative base excess is equivalent to an acid excess.
Normal: -3 to +3 mmol/L
Metabolic acidosis: < -3 mmol/L
Metabolic alkalosis: > +3 mmol/L
Base excess (BE) is the mmol/L of base that needs to be removed to bring the pH back to normal when PCO2 is corrected to 5.3 kPa or 40 mmHg. During the calculation any change in pH due to the PCO2 of the sample is eliminated, therefore, the base excess reflects only the metabolic component of any disturbance of acid base balance.

32. AG (anion gap)
Difference between undetermined anions and undetermined cations.
Anion gap = Na+ - [Cl¯ + HCO3¯]
Based on the principle of electrical neutrality, the serum concentration of cations (positive ions) should equal the serum concentration of anions (negative ions). However, serum Na+ ion concentration is higher than the sum of serum Cl¯ and HCO3¯ concentration. Na+ = Cl¯ + HCO3¯ + unmeasured anions (gap).
Normal: 122mmol/L ( mmol/L)
These “undetermined anions” are generally accounted for by negatively charged proteins, phosphate, sulfate and organic anions. Except for a few relatively uncommon circumstances, an increase in the AG is synonymous with the accumulation of nonvolatile acids in body fluids, and suggests metabolic acidosis.

33. pH—Determine Acidosis versus alkalosis
Determine Metabolic
——the concentration of HCO3¯, controlled by non-respiratory factors.
SB (standard bicarbonate)
BE (base excess)
Determine Respiratory
——the concentration of CO2。
PaCO2
HCO3¯—influenced by Metabolic and Respiratory factors。
AG — ■ Helpful in Metabolic Acidosis
■ Helpful in mixed acid-base disorders

34. Once the acid-base disorder is identified as respiratory or metabolic, we must look for the degree of compensation that may or may not be occurring. This compensation may be complete (pH is brought into the normal range) or partial (pH is still out of the normal range but is in the process of moving toward the normal range.)
In pure respiratory acidosis (high PaCO2, normal [HCO3¯], and low pH) we would expect an eventual compensatory increase in plasma [HCO3¯] that would work to restore the pH to normal. Similarly, we expect respiratory alkalosis to elicit an eventual compensatory decrease in plasma [HCO3¯].
A pure metabolic acidosis (low [HCO3¯], normal PaCO2, and a low pH) should elicit a compensatory decrease in PaCO2, and a pure metabolic alkalosis (high [HCO3¯], normal PaCO2, and high pH) should cause a compensatory increase in PaCO2.
All compensatory responses work to restore the pH to the normal range ( )

35. Pathogenesis of Acid Base disorders

36. Metabolic acidosis Acids  Primary [HCO3] Increased AG Source
Lactic acidosis
generate
Source
ketoacidosis
Increased AG
Acids
Fixed acids
Salicylic acidosis
intake
Exclusion
：renal failure 
Source 
—— impossible
From GI：diarrhea
Bases
Normal AG
Loss 
From kidney：proximal/distal tubular acidosis
Consume 
：ammonium chloride have been administered

37. Metabolic alkalosis   Primary [HCO3] Fixed acids Bases Source 
——impossible
Fixed acids
From GI
：vomiting, gastric suction
K+ or Cl¯ deficiency
Loss 
Hyperaldosteronism
Cushing’s syndrome
From kidney
Diuretic therapy
Source 
——Alkali administration：NaHCO3、sodium lactate .
Bases 
Exclusion 
——impossible

38. Severe vomiting Loss of H+  Loss of Cl Loss of K+ Loss body fluid
Ald 

39. Respiratory alkalosis
Respiratory acidosis
Primary [H2CO3 ]  
Generation
——impossible
Volatile acid
Exhalation 
：failure of ventilation
inhalation
：inhale CO2 at high concentration
Respiratory alkalosis
Primary [H2CO3 ]  
Generation 
——impossible
Volatile acid
Exhalation 
hypoxemia, anxiety, hysteria,
Salicylate intoxication
CNS diseases

40. Compensation to acidosis
metabolic respiratory
Feature HCO3-，BB,SB,AB,BE(－) H2CO3 ，PaCO2 AB>SB
Blood HA + HCO3-A-+ H2CO plasma protein, RBC Hb
buffering  (No compensation to acute
CO2 + H2O repiratory acidosis)
Lung increased breathing no compensation
(Kussmaul Respiration)
ICF H+ + KPrK++ HPr；
buffering H+ + K2HPO4K++ KH2PO4 ；
[K+ ]e
Kidney unless the acidosis is due to renal dysfunction,
the kidneys respond by increasing hydrogen ion secretion and
ammonia production, this result in HCO3¯ reabsorption.
Bone Ca3(PO4)2 + 4H+3Ca2+ + 2H2PO4-
Results PaCO2, HCO3- recovery BB,SB,AB,BE(+)

41. Compensatory Responses: Metabolic Acidosis
In general, respiratory compensation results in a 1.2 mmHg reduction in PCO2  for every 1.0 meq/L reduction in the plasma HCO3- concentration down to a minimum PCO2 of 10 to 15mmHg.  
For example, if an acid load lowers the plasma HCO3- concentration to 9 meq/L, then: Degree of HCO3- reduction is  24 (optimal value) – 9 = 15. Therefore, PCO2 reduction should be  15 × 1.2 =  18. Then PCO2 measured should be 40 (optimal value) – 18 = 22mmHg.
 Winter's Formula To estimate the expected PCO2 range based on respiratory compensation, one can also use the Winter's Formula which predicts: PCO2 = (1.5 × [HCO3-]) + 8 ± 2
Therefore in the above example, the PCO2 according to Winter's should be (1.5 × 9) + 8 ± 2 = 20-24
 Another useful tool in estimating the PCO2 in metabolic acidosis is the recognition that the pCO2 is always approximately equal to the last 2 digits of the pH.

42. Compensation to alkalosis
metabolic respiratory
Feature HCO3-，BB,SB,AB,BE(＋) H2CO3 ，PaCO2， AB<SB
Blood limited effect on alkali HCO3- enter RBC；CO2 diffuse in plasma
Buffering OH-+ H2CO3(HPr)HCO3-(Pr-)+ H2O HCO3-＋HBuf  H2CO3＋Buf－
Lung PH（H+）  deceased breathing
CO2 exhalation PaCO2 no compensation
ICF H+K+ exchange, [K+]，
Buffering oxygen dissociation curve left shift, glucolysis , H+ 。
Kidney excrete the excess load of HCO3¯
Results H2CO3，HCO3- recovery chronic：BB、SB、 BE(-)

43. Compensatory Responses: Metabolic Alkalosis
On average the pCO2 rises 0.7 mmHg for every 1.0 meq/L increment in the plasma [HCO3-].
For example, if an alkali load raises the the plasma HCO3- concentration to 34 meq/L, then: Degree of HCO3- elevation is  34 – 24 (optimal value)= 10.
Therefore, PCO2 elevation should be  0.7 × 10 =  7. Then PCO2 measured should be 40 (optimal value) +7 = 47mmHg.

44. Effects of Acid Base disorders

45. Effects of acidosis Respiratory Effects
Hyperventilation ( Kussmaul respirations)
Shift of oxyhaemoglobin dissociation curve to the right
Decreases 2,3 DPG levels in red cells, which opposes the effect above. (shifts the ODC back to the left) This effect occurs after 6 hours of acidemia.
Cardiovascular Effects
Depression of myocardial contractility (this effect predominates at pH < 7.2 )
Sympathetic over-activity ( tachycardia, vasoconstriction, decreased arrhythmia threshold)
Resistance to the effects of catecholamines (occur when acidemia very severe)
Peripheral arteriolar vasodilatation ■ Venoconstriction of peripheral veins
Vasoconstriction of pulmonary arteries ■ Effects of hyperkalemia on heart
Central Nervous System Effects
Cerebral vasodilation leads to an increase in cerebral blood flow and intracranial pressure (occur in acute respiratory acidosis)
Very high pCO2 levels will cause central depression
Other Effects
Increased bone resorption (chronic metabolic acidosis only)
Shift of K+ out of cells causing hyperkalemia (an effect seen particularly in metabolic acidosis and only when caused by non organic acids)
Increase in extracellular phosphate concentration

46. Increased rate and depth of breathing ("Kussmaul breathing")
Decreased heart rate (bradycardia)

47. Effects of alkalosis
Respiratory Effects
Shift of oxyhaemoglobin dissociation curve to the left (impaired unloading of oxygen
The above effect is however balanced by an increase in 2,3 DPG levels in RBCs.
Inhibition of respiratory drive via the central & peripheral chemoreceptors
Cardiovascular Effects
Depression of myocardial contractility
Arrhythmias
Central Nervous System Effects
Cerebral vasoconstriction leads to a decrease in cerebral blood flow (result in confusion, muoclonus, asterixis, loss of consciousness and seizures) Only seen in acute respiratory alkalosis. Effect last only about 6 hours.
Increased neuromuscular excitability ( resulting in paraesthesias such as circumoral tingling & numbness; carpopedal spasm) Seen particularly in acute respiratory alkalosis.
Other Effects
Causes shift of hydrogen ions into cells, leading to hypokalemia.
Note: Most of the above effects are short lasting.

48. Mixed acid base disorders
The simple, or primary, acid-base disorders (respiratory and metabolic acidosis and alkalosis) evoke a compensatory response that produces a secondary acid-base disturbance and reversion of the blood pH towards (rarely to) normal; e.g., a simple metabolic acidosis will result in a secondary respiratory alkalosis, both of which will ordinarily be reflected in the patients’ acid-base-related analytes in blood. When two primary acid-base disturbances arise simultaneously in the same patient, the complex is called a mixed acid-base disorder. If three primary disturbances occur together, the patient is described as having “triple acid-base disorder.”
More than one acid base disturbance present. pH may be normal or abnormal.

50. Case study
A 50 year old insulin dependent diabetic woman was brought to the ED by ambulance. She was semi-comatose and had been ill for several days. Current medication was digoxin and a thiazide diuretic for CHF.
Lab results
Serum chemistry: Na 132, K 2.7, Cl 79, Glu 815,
Lactate urine ketones 3+
ABG: pH PCO HCO3¯ pO2 82  
 What is the acid base disorder? Why?

51. Thank You