Acid Base Regulation

and
its Disorders
EMERGENCY
INTENSIVE CARE UNIT

NICU

PICU
BLOOD INVESTIGATIONS
• Normal pᴴ of blood - 7.4
• Range - 7.35 -7.45
• Blood pᴴ compatible to life is - 6.8-7.8
• Any increase or decrease - DEATH
Normal pᴴ required for normal cellular activities

any changes in blood pᴴ

alters intracellular pᴴ

cellular metabolic activities are altered, due to distortion

of protein structures

Affects enzyme activity adversely

• Maintenance of blood pᴴ with in this narrow
range 7.35-7.45 is an important homeostatic
mechanism regulated by the body.
3 mechanisms.
 Blood Buffers
 Respiratory mechanism
 Renal mechanism
 The mechanism of regulation of blood pᴴ
involves
first line defence – immediate
temporary solution

1. Blood Buffer systems in the blood - which

restricts pᴴ change in the body fluids
2. Respiratory mechanism- regulation of
excretion of CO₂ and hence, regulation of
H₂CO₃ concentration in ECF.
second line defence - Delayed

Permanent solution

achieved by the kidneys (Renal mechanism) which

involves excretion of excess of acid/base and thus
ultimate regulation of concentration of H⁺ and HCO₃‾
ions in ECF
 Blood Buffers
Contains 3 Buffers system
• Bicarbonate buffer
• Phosphate buffer
• Protein buffer
Each buffer system consists of a mixture of a
weak acid and its salt with strong base which
has the ability to resist change in the H⁺ ion
concentration and thus prevent any change of pᴴ
of the medium.
 Blood Buffers.....
Cont
Buffer systems respond immediately by
• Addition of acid/ base
• They do not remove acids from the body.
• Cannot replenish the alkali reserve of the body
According to Henderson's – Hasselbachs equation
pᴴ = pᵏᵃ + log conjugated base
undissociated acid
pᴴ= negative log of Hᶧ ions
pᵏᵃ = dissociation constant of weak acid
 Bicarbonate buffer

• [Base] = [NaHCO₃]
[Acid ] [H₂CO₃]
• most predominant buffer system of the ECF
particularly plasma
• which consist of weak acid(H₂CO₃) and its
corresponding salt with strong base(HCO₃‾ )
• Normal ratio in blood = [NaHCO₃] i.e 20
[H₂CO₃] 1
• According to HHB equation for bicarbonate buffer

pH = pka+ log HCO₃⁻ Substituting the values

H₂CO₃
pᵏᵃ for H₂CO₃ =6.1
HCO₃ˉ = 24 mmol/L
H₂CO₃ = 1.2 mmol/L
 Bicarbonate buffer......
Cont
• plasma[HCO₃⁻] = 24 mmol/L (22-26 mmol/L)
• Carbonic acid is a solution of CO₂ in water its
concentration is given by the product of pco2
(arterial partial pressure of CO₂ = 40 mmHg)
and solubility constant of CO₂ (0.03)
• 40X 0.03 = 1. 2 mmol/L
We get pᴴ = 7.4 i.e
pᴴ= 6.1+ log 24
1.2
= 6.1+ log20
=6.1+ 1.3
=7.4
Hence for the blood pH of 7.4
The ratio of bicarbonate to carbonic acid is 20:1
 Bicarbonate buffer......
Cont
• i.e the concentration of HCO₃⁻ is 20 times
higher when compared to concentration of
carbonic acid in blood ----referred to as
ALKALI RESERVE and is responsible for the
effective buffering of Hᶧ ions produced in the
body.
 Phosphate buffer[Na₂HPO₄]
[NaH₂PO₄]

• Disodium hydrogen phosphate and sodium

dihydrogen phosphate constitutes the po4
buffer
• It is mainly an Intra cellular buffer
• The concentration of the buffer is very low in
the plasma(otherwise it would have been the
most effective buffer in plasma because the pka
value 6. 8 is very near to the physiological pᴴ of
7.4)
• According to HHB equation for phosphate buffer
pH = pka + log Na₂HPO₄
NaH₂PO₄
7.4=6.8+log[ Base]
[acid]
7.4-6.8=log [Base]
[acid]
0.6= log [Base]
[acid]
Antilog 0. 6= 4
Hence it is estimated that the ratio of base to acid for
phosphate buffer is 4.
 Protein buffer system
• Buffering capacity is only 1-2%
• The plasma proteins and Hb together
constitute protein buffer system of the blood
• Buffering capacity of proteins depends on pka
value of ionizable group of amino acids
• The imidazole group of histidine {having pka
of 6.7} is the most effective contributor of
protein buffer
 Protein buffer......
cont
• Hb of RBC is also an important blood buffer.
• Each Hb molecule has 38 Histidine residues.
• It mainly buffers the fixed acids, besides being
involved In the transport of gases(O₂ ,CO₂)
• Discussed in detail under Respiratory
mechanism
 Respiratory mechanism- Lungs
• Rapid mechanism for the maintenance of acid
base balance which is achieved by regulating
the concentration of H₂CO₃ in the blood.
• O₂ is transported from the lungs to the tissue
& CO₂ formed during cellular metabolic
activities diffuses out of the cells into the ECF
& reaches the lungs.
 Respiratory mechanism- Lungs
cont....
• Rate of respiration is controlled by the
chemoreceptors in the Respiratory centers
located in the medulla of the brain.
• This centre is highly sensitive to changes in
blood pᴴ.
 Respiratory mechanism- Lungs
cont....

Chemoreceptor Respiratory
pH ↓ s stimulated rate ↑

CO2 washout hyperventilation

 Respiratory mechanism- Lungs
cont....

pH Chemoreceptors Respiratory
↑ suppressed rate ↓

CO2
retained hypoventilation
 Respiratory mechanism- Lungs
cont....
• Hb buffer in the RBC has an important role in respiratory regulation
of pᴴ.
• At the tissue level-----> due to cellular metabolic activities co2 is
continously being formed which gets hydrated to form carbonic acids
which in turn dissociates to release H+ ions and HCO3-(diffuses out
into the plasma)
• Due to decreased O2 tension, the oxyHb dissociates delivering O2 to
the cells, forming deoxyHb which combines with H+  reduced Hb
(Hhb)
• In the lungs - formation of oxyHb from reduced Hb result in the
formation of H+ ions combines with HCO₃ˉ to form
H₂CO₃ . Since the concentration of carbondioxide is low in the lungs 
the equilibrium shifts towards the formation of carbondioxide which is
continously eliminated via the lungs
 ISOHYDRIC SHIFT/ TRANSPORT
During the above process very little change in
pH occurs because of the newly formed H+
ions which are being buffered by the
formation of very weak acid ……. This is
reffered to as Isohydric Shift
Respiratory mechanism- Isohydric shift
Generation of HC0₃ˉ by RBC’s Chloride shift
 Generation of HC0₃ˉ by RBC’s
chloride shift
• Due to lack of aerobic metabolic pathways,
RBC produce very little CO₂.
• The plasma CO₂ diffuses into RBC along the
concentration gradient where it combines
with H₂O to form H₂CO₃ by
carbonic anhydrase.
• In RBC, H₂CO ₃ dissociates to produce Hᶧ and
HCO₃ ˉ
 Respiratory mechanism- Lungs
cont....
• H⁺ are trapped and buffered by Hb.
• As the concentration of HCO₃ˉ increases in
RBC’s it diffuses into plasma along the
concentration gradient in exchange for Clˉ
ions, to maintain electrical neutrality ---->
CHLORIDE SHIFT which helps to generate
HCO₃ˉ .
 RENAL MECHANISM - KIDNEYS
• Delayed but permanent solution to acid base
disturbances
• Kidney regulates the blood pᴴ by maintaining
the alkaline reserve, besides excreting/
reabsorbing the acidic/basic substance, as
the situation demands.
 RENAL MECHANISM...
cont
• Urine pᴴ normally lower than blood pᴴ.
• pᴴ of urine is (6.0) this clearly indicates that the
kidneys have contributed to the acidification
of urine, when it is formed from blood plasma
(pᴴ=7).
• In other words, the Hᶧ ions generated in the
body in the normal circumstances, are
eliminated by acidified urine. Hence urine pᴴ is
acidic.
 Renal regulation
• Carbonic anhydrase plays an important role
in renal regulation of pᴴ which occurs by the
following mechanisms
1. Excretion of Hᶧ ions
2. Reabsorption of HCO₃⁻
3. Excretion of titratable acid
4. Excretion of ammonium ions
Excretion of H+

+
Buffer

H+Buffer
Excreted
in urine
 Excretion of Hᶧ ions
• Kidney is the only route through which Hᶧ can
be eliminated from the body(Hᶧ excretion
occurs in the proximal CT ) and is coupled with
the regeneration of HCO₃⁻ as follows:
• CA catalyses the production of H₂CO₃ from CO₂
and H₂O in the renal tubular cell. H₂CO₃ then
dissociates to form Hᶧ and HCO₃ˉ.
• H+ ion is secreted into the tubular lumen in
exchange with sodium.
 Excretion of Hᶧ ions....
cont
• The Naᶧ is associated with HCO₃ˉ is
reabsorbed into the blood. This is an effective
mechanism to eliminate acid(H⁺) from the
body with a simultaneous generation of HCO₃ˉ
which adds up to the alkali reserve of the
body. Hᶧ combines with non- carbonate base
and is excreted in urine.
Reabsorption of
 
 Excretion of Hᶧ ions....
cont
• HCO₃⁻ freely diffuse from the plasma into the
tubules. Here HCO₃⁻ combines with Hᶧ secreted by
tubular cells, to form H₂CO₃ is then cleared by CA to
form CO₂ and H₂O.
• As the CO₂ concentration builds up in the lumen it
diffuses into the tubular cells along the
concentration gradient.
• In the tubular cells, CO₂ again combines with H₂0 to
form H₂CO₃ which then dissociates into Hᶧ and
HCO₃⁻.
 Excretion of Hᶧ ions....
cont
• Then Hᶧ is secreted into the lumen in exchange
for Naᶧ. This HCO₃ˉ is reabsorbed into plasma
in association with Naᶧ. Reabsorbed HCO₃ˉ is a
cyclic process with net excretion of Hᶧ.
Excretion of Titratable acid
 Excretion of titratable acid
• Titratable acidity is a measure of acid excreted into
urine by the kidney which can be estimated by
titrating urine back to normal pᴴ of blood.
Titratable acidity refers to the number of ml of N/10
NaOH required to titrate 1 Lt urine to blood pH.
• Hᶧ ions is secreted into the tubular lumen in
exchange for Naᶧ ions. Naᶧ is obtained from the
base, disodium HPO₄,later in turn combines with Hᶧ
to produce the acid NaH₂P in which form the major
quantity of titrable acid in urine is present,
 Excretion of titratable acid......
cont
• As the tubular fluids move down the renal
tubules, more and more Hᶧ ions are added
resulting in acidification of urine.
Excretion of Ammonium ions
 Excretion of ammonium ions
• Effective method to eliminate excess acid
produced in the body.
• Renal tubular cells deaminate glutamine to
glutamate and NH₃ catalyzed by glutaminase.
• NH₃ liberated diffuse into the tubular lumen
where it combines with Hᶧ to form NH₄ᶧ.
• Ammonium ions cannot diffuse back into tubular
cells and are therefore excreted in urine.
• CO₂ combines with H₂O to form H₂CO₃ which
dissociates to form HCO₃ and Hᶧ interaction
between lungs, RBC and in handling CO₂ to
maintain pᴴ of blood is shown in CO₂
generated by aerobic metabolism may be
exhaled by lung or compensated to HCO₃ by
RBC’s and kidney to add up the alkali reserve
of the body.
ABG ANALYSER
Normal ABG values
 Acid base disorders
pH

Low Acidosis High Alkalosis

High pCO 2
Respiratory
acidosis
Low HCO3 Metabolic acidosis High HCO3 Metabolic Alkalosis
 Disorders of acid base balance
• 4 acid base disorders which are generally due to
alterations in either HCO₃‾ or H₂CO₃.
• Metabolic Disorders are due to alteration in
HCO₃‾concentration
• Respiratory Disorders are due to alteration in H₂CO₃
level.
• To counter the AB disturbances the body gears up its
homeostatic mechanism and makes an attempt to
restore the pH to normal level(7.4) referred to as
COMPENSATION
 COMPENSATION
PARTIAL
• Compensation
COMPLETE/ FULLY

• For Acute Metabolic Disorders (HCO₃‾ ) 

Respiratory Compensation sets in & regulates
the H₂CO₃ (CO₂) by Hyperventilation/
Hypoventilation.
• For Acute Respiratory Disorders (H₂CO₃) 
Renal Compensation sets in & regulates
reabsorption of HCO₃‾ ; pH tend to restore.
 METABOLIC ACIDOSIS
• Most commonest
• Pᴴ - ↓
• [HCO₃⁻] - ↓

•Acids get accumulated

•HCO₃⁻ from alkali reserve used up - ↓ [HCO₃⁻]
 Metabolic acidosis….
cont
• primary base deficit - ↓ [HCO₃‾ ]

1. Its utilisation in buffering H+

2. Loss in urine / GIT
3. Failure to regenerate
 METABOLIC ACIDOSIS - CAUSES
1. Endogenous excess production of acids
2. Ingestion/ administration of acids
3. Renal insufficiency
4. Abnormal loss of [HCO₃⁻]
 METABOLIC ACIDOSIS – CAUSES……
cont
1. Endogenous excessive production of acids which
combines with NaHCO₃ & depletes the alkali reserve
 Diabetic ketoacidosis [severe uncontrolled DM]
 Lactic acidosis
 Prolonged Starvation
 Hyperpyrexia
 High fibre
 Violent exercise
 Shock, anoxia etc
 METABOLIC ACIDOSIS – CAUSES……
cont
2. Ingestion / administration of excessive
quantities of acids like
 Acetyl salicylic acid
 Phosphoric acid
 HCl, NH₄Cl, Mandelic acid
 METABOLIC ACIDOSIS – CAUSES……
cont
3.Renal insufficiency
 Terminal stage of nephritis
 Destructive renal lesions-
Polycystic kidney Disease
Pyelonephritis
Hydronephrosis
Renal TB
 METABOLIC ACIDOSIS – CAUSES……
cont
4. Abnormal loss of [HCO3ˉ] -
Severe Diarrhoea
Small Bowel Fistula
Biliary Fistula
 Compensation
• In Metabolic acidosis - Respiratory compensation
sets in
Respiratory centres +

Hyperventilation

Increased elimination of CO₂

[H₂CO₃] ↓
 Metabolic acidosis - ANION GAP
• Sum of Cations = sum of Anions in ECF
(maintain electrical neutrality)
• Cations - Na⁺ & K⁺ = 95% commonly
• Anions - Cl⁻ & HCO₃⁻ = 86% measured

• Hence there is difference between the

measured cations and anions.
 ANION GAP….
cont
• The unmeasured Anions constitutes the Anion
Gap which is due to the presence of
protein anions, sulphates, phosphates and
organic acids.
• Anion gap is calculated as the difference
between (Na⁺ & K⁺) and (HCO₃⁻ & Cl⁻)
• Normal anion gap is 12 mmol/L
 Anion Gap – 2 types
• High Anion Gap Metabolic Acidosis [HAGMA]
Renal Failure
Diabetic ketoacidosis
Lactic acidosis
• Normal Anion Gap Metabolic Acidosis[NAGMA]
Diarrhea
Hyperchloremic Acidosis
Renal Tubular Acidosis
 Respiratory acidosis

Defect
• pᴴ - ↓
• [H₂CO₃] - ↑
 RESPIRATORY ACIDOSIS - CAUSES
1.Pulmonary disorders (loss of ventilatory function
or there is impaired diffusion of CO₂ across
alveolar membrane)
• Bronchial asthma
• Bronchopneumonia
• Pneumothorax
• Emphysema
• Pulmonary oedema
• Mediastinal tumour
 RESPIRATORY ACIDOSIS – CAUSES....
Cont
2. Breathing air with high content of CO₂
3. Depression of Respiratory Centre by drugs -
Morphine,
Barbiturates
 COMPENSATION BY KIDNEYS

• HCO₃‾ is generated & retained by the

kidneys
• Excretion of titratable acid & NH₄ is
increased in urine
 Metabolic Alkalosis
DEFECT
• pH - ↑
• [ HCO₃‾ ] - ↑
 Metabolic Alkalosis- Causes
• Excessive vomiting (loss of H⁺) –
• Increase HCl loss from the stomach
- Pyloric Obstruction,
- Improper Gastric Lavage
• Excessive intake of sodium bicarbonate in
treatment of gastric acidity.
 Compensation by Lungs
Inhibition of Respiratory Center

Hypoventilation

Retention of CO₂

↑ [H2CO3]
 RESPIRATORY ALKALOSIS
DEFECT
• pᴴ - ↑
• [ H₂CO₃] - ↓
 Causes :
Prolonged hyperventilation seen in
• Hyperpyrexia
• Hysteria
• Hypoxia
• Salicylate poisoning
• CNS disease {meningitis, encephalitis}
 RESPIRATORY ALKALOSIS
COMPENSATION.....KIDNEYS
Renal mechanism tries to compensate by
• Increase excretion HCO₃‾
• Decreased excretion of NH₄ in urine
• Retention of Cl in blood
 Clinical Case 1
A elderly diabetic is found non responsive /
unconscious , his blood investigations reveal high
blood sugar level 800 mg/dl , urinary ketone bodies
present
• Blood pH : 7.12
• pCO2 : 42 mmHg
• Bicarbonate : 18 mmoles/L

• Diagnosis : Metabolic Acidosis

 Clinical Case 2
A first time mountain climber after 1000 feet ascension develops
light headedness , difficulty breathing , numbness & tingling ,
hyperventilation

• Blood Ph : 7.52
• pCO2 : 30 mmHg
• Bicarbonate : 23 mmoles/L

• Diagnosis : Respiratory Alkalosis

 Clinical Case 3
A new mother complains , her new born is repeatedly
vomiting feeds,
The enthusiastic intern checks ABG to confirm the diagnosis
of pyloric stenosis

• Blood pH : 7.52
• pCO2 : 42 mmHg
• Bicarbonate : 40 mmoles/L

• Diagnosis : Metabolic alkalosis

 Clinical Case 4
A patient was rushed to the casualty with the history
of trauma to the chest at the work place ,after
examination : Pneumothorax was diagnosed

• Blood pH : 7.2
• pCO2 : 70 mmHg
• Bicarbonate : 22 mmoles/L

• Diagnosis : Respiratory acidosis

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