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Acid-Base Disturbance
Department of Pathophysiology
Shanghai Jiao-Tong University School of Medicine
main topics
 Acid Base Physiology
 Acid Base disturbances
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
The concept of Acid Base balance
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.
acids?
Any ionic or molecular substance
that can act as a proton donor.
Strong acid:HCl, H2SO4, H3PO4.
Weak acid:H2CO3, CH3COOH.
bases?
Any ionic or molecular substance
that can act as a proton acceptor.
Strong alkali:NaOH, KOH.
Weak alkali:NaHCO3, NH3, CH3COONa.
Origin of acids
Much more
Intracellular metabolism
Volatile
acids
Fixed
acids
CO2+H2O=H2CO3
Lactic acid
Ketone bodies
Sulfuric acid
Phosphoric acid
Origin of bases
less
300~400L CO2 (15mol H+)
50~100 mmol H+
NH3 , sodium citrate, sodium lactate
Acid Base balance & regulation
pH
- pH of ECF is between 7.35 and 7.45.
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.
 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.
H+ load
ECF
Buffers
RBC
lung
Respiratory
control
ICF
H+-K+
exchange
Hb
others
buffers
H2CO3 CO2
Renal
H+ excretion
bicarbonate
reabsorption
minutes
hours
Release
bone salt
Ca2++H2PO4
Buffers
Acid
excretion
In chronic
metabolic
acidosis
days
Very slow
Expiration
Immediately
Bone
Buffering system
 ECF
Plasma
NaHCO3/ H2CO3
intercellular
fluid
NaHCO3/ H2CO3
 ICF**
KPr/HPr
NaPr/HPr*
Na2HPO4/NaH2PO4
Na2HPO4/NaH2PO4
K2HPO4/KH2PO4
KHCO3 /H2CO3
organic acids
 RBC
KHb/HHb
KHbO2/HHbO2
KHCO3/ H2CO3
* HPr:protein; ** muscle cells。
K2HPO4/KH2PO4
buffering?

H+ + A
HA
[ H+ ]  [ A ]
Ka =
[
H+ ]
[ HA ]
= Ka 
pH = pKa + lg
[ HA ]
[ A ]
[ A ]
[ HA ]
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)
Primary
changing
CO2
CO2 + H2O
CA
H2CO3
CA
plasma
HCO3
Cl
HCO3

Cl
RBC
H+

Hb buffering
Cl¯ transfer
CA :carbonic anhydrase
The compensation effect of RBC
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.
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.
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.
Summary
uBuffers
solution.
only provide a temporary
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.
Acid base disturbance
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.
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 = 6.1 + 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¯]).
Acid Base parameter
/Arterial Blood Gases (ABGs)
Arterial Blood Gas Sampling
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 7.35 - 7.45:
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.
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”.
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).
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.
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 (10 - 14 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.
pH—Determine Acidosis versus alkalosis
Determine Metabolic
Determine Respiratory
——the concentration of
——the
HCO3¯, controlled by non-
CO2。
concentration
of
respiratory factors.
PaCO2
SB (standard bicarbonate)
BE (base excess)
HCO3¯—influenced by Metabolic and Respiratory factors。
AG — ■ Helpful in Metabolic Acidosis
■ Helpful in mixed acid-base disorders
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 (7.35 - 7.45)
Pathogenesis of Acid Base
disorders
Metabolic
acidosis
Lactic acidosis
Source ketoacidosis
Fixed acids
Salicylic acidosis
intake
Exclusion :renal failure
Source 
Bases
Loss 
 —— impossible
From GI:diarrhea
From kidney:proximal/distal tubular acidosis
Consume  :ammonium chloride have been administered
Normal AG
Acids
generate
Increased AG
Primary [HCO3]
Metabolic
alkalosis
Primary [HCO3]
Source 
 ——impossible
From GI :vomiting, gastric suction
Fixed acids
K+ or Cl¯ deficiency
Loss 
From kidney
Hyperaldosteronism
Cushing’s syndrome
Diuretic therapy
Source  ——Alkali administration:NaHCO3、sodium lactate .
Bases
Exclusion 
 ——impossible
Loss of H+
Severe
vomiting
Loss of Cl
Loss of K+
Loss body fluid
Ald 
Respiratory
acidosis
Primary [H2CO3 ] 
Generation
Exhalation  :failure of ventilation
Volatile acid
inhalation
Respiratory
alkalosis
:inhale CO2 at high concentration
Primary [H2CO3 ] 
Generation 
Volatile acid
 ——impossible
 ——impossible
Exhalation  hypoxemia, anxiety, hysteria,
Salicylate intoxication
CNS diseases
Compensation to acidosis
metabolic
Feature
Blood
buffering
respiratory
HCO3-,BB,SB,AB,BE(-)
HA + HCO3-A-+ H2CO3

CO2 + H2O
Lung
H2CO3 ,PaCO2 AB>SB
plasma protein, RBC Hb
(No compensation to acute
repiratory acidosis)
increased breathing
no compensation
(Kussmaul Respiration)
ICF
buffering
H+ + KPrK++ HPr;
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
Results
Ca3(PO4)2 + 4H+3Ca2+ + 2H2PO4PaCO2, HCO3- recovery
BB,SB,AB,BE(+)
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 HCO3concentration 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.
Compensation to alkalosis
metabolic
Feature
Blood
respiratory
HCO3-,BB,SB,AB,BE(+)
limited effect on alkali
H2CO3 ,PaCO2, AB<SB
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
ICF
Buffering
Kidney
Results
no compensation
H+K+ exchange, [K+],
oxygen dissociation curve left shift, glucolysis , H+ 。
excrete the excess load of HCO3¯
H2CO3,HCO3- recovery
chronic:BB、SB、 BE(-)
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.
Effects of Acid Base disorders
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
Increased rate and depth of
breathing ("Kussmaul breathing")
Decreased
heart rate
(bradycardia)
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.
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.
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 0.9 urine ketones 3+
ABG: pH 7.41 PCO2 32 HCO3¯ 19

pO2 82
What is the acid base disorder? Why?

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