REGULATION OF ACID BASE
BALANCE:
It means regulation of pH of body fluids.
pH = -log [H+]
pH of arterial blood = 7.4
pH of venous blood = 7.35 (because of dissolved CO2)
Why it is important to regulate pH??
• It is important to regulate pH because enzymes
in body need optimal pH & when pH changes,
there is marked effect on activity of enzymes.
• When pH is >7.45, it is ALKALOSIS
• When pH is <7.35, it is ACIDOSIS
• In which range of pH, person can survive?
• Survival range: (very narrow range)
• pH of body fluids depend upon BUFFERS in
body fluids.
• What is a BUFFER SYSTEM?
• Buffer system is a solution which minimize or resist change in pH (IT
CANNOT PREVENT THE CHANGE!!!)
• A buffer system consists of a weak acid & its salt (mostly) or a weak
alkali & its salt, e . g,
HCO3- buffer:
• salt is NaHCO3 & weak acid is H2CO3
• It may be KHCO3 salt…..but in plasma & ECF main cation is Na+
• Another e . g, is
PO4 --- buffer:
• salt is Na2HPO4 & acid is NaH2PO4
• ACID: Which can donate H+
• BASE: Which can accept H+
BUFFERS:
• 1) BLOOD (Plasma & RBCs)
• 2) IN ISF
• 3) IN ICF
BLOOD BUFFERS:
• 1) HCO3 BUFFER
• 2) PO4 BUFFER
• 3) PROTEIN BUFFER
• 4) Hb BUFFER IN RBCs
HCO3 BUFFER IN BLOOD:
• It consist of HCO3 (salt) & acid (H2CO3 which is
dissolved CO2).
• HCO3 means NaHCO3 because Na+ is main cation in
plasma.
• Ratio = salt/acid = NaHCO3/H2CO3
= 20/1
pka of this buffer system (HCO3) = 6.1
6.1 + log20 = 6.1 + 1.3 = 7.4
pka = -log of dissociation constant of acid
HENDERSON HASSEL BALCH
EQUATION:
• pH = pka + log [salt / acid]
• pka is –log of dissociation constant of acid
• HCO3 buffer system:
for HCO3-, pka = 6.1
so 6.1 + log salt or HCO3
Acid
= 6.1 + log 24mEq or mM/L
1.2mEq or mM/L
= 6.1 + log 20
= 6.1 + 1.3 = 7.4
When ratio between salt & acid is 20, pH will be 7.4.
PO4 BUFFER IN BLOOD:
• SALT= Na2HPO4
• ACID= NaH2PO4
• Ratio=salt/acid = 4/1
• Pka of H3PO4 = 6.8
PROTEIN BUFFER IN BLOOD:
• SALT=Na-Proteinate
• ACID=Acid Protein or H-Protein
Hb BUFFER IN RBCs
• Cation in RBCs = K+
• For Hb buffer, salt = K-Hemoglobinate
• Acid = Acid Hemoglobin=HHb
• Hb is very important buffer in blood
BUFFERS IN ISF:
• HCO3
• PO4
• Weak protein buffer
BUFFER IN ICF:
• Main buffer in ICF is protein buffer.
• Buffering power of a buffer depends on 2 factors:
1) conc. of buffer (quantitative)
2) pka (qualitative)
If conc. is greater, stronger will be the buffer.
If pka of buffer is near to pH of blood, stronger will be
that buffer.
If we compare HCO3 & PO4 buffer, quantitatively
powerful is HCO3 buffer.
Its conc. is 10x more than PO4 buffer.
Qualitatively, PO4 buffer is more powerful, as 6.8 is closer
to 7.4 than 6.1.
Sources of H+ or acid in the body:
1) OXIDATION OF CARBON CONTAINING
COMPOUNDS:
• Gives rise to CO2 (Volatile acid).
• During exercise production of CO2 increases very
much.
2) FORMATION OF NON-VOLATILE OR
ORGANIC ACIDS DURING
METABOLISM OF CHO, FATS & PROT.
- Most of these acids are further oxidized to form CO2 &
H2O, but their level increase in the blood when there is
increased rate of metabolism.
- In hypoxia  increased production of these acids. (to
provide energy, rapid metabolism)
- Certain drugs & disorders can increase their
production.
- These acids are PYRUVIC ACID, LACTIC ACID, ACETOACETIC ACID & BETA HYDROXY BUTYRIC ACID.
3) FORMATION OF H2SO4:
• When S containing compounds (like Cysteine
& Methionine) are oxidized, H2SO4 is
produced.
4) FORMATION OF H3PO4:
• When phospho-esters, phosphatides.
Phospho-proteins & nucleo-proteins are
hydrolyzed in the body.
4) Small amount of some acids are
INGESTED BY MOUTH:
• Like NH4Cl in cough syrup (noshadir)  mild
acidosis.
BUFFERING MECHANISMS IN THE BODY:
(2 TYPES)
• 1) PHYSICO-CHEMICAL BUFFERING
• 2) PHYSIOLOGICAL BUFFERING
PHYSICO-CHEMICAL BUFFERING:
• Most immediate buffering. (when an acid or alkali is
added to body fluids, it is the 1st line of defense against
disturbance of acid base balance.
A) PHYSICO-CHEMICAL BUFFERING OF CO2/VOLATILE
ACID:
CO2 is transported as HCO3 & in free form. From
tissues, CO2  RBCs.
In RBCs, CO2 + H2O  H2CO3
H2CO3 (unstable)  H + HCO3
H ion + Hb  HHb (buffered by Hb to form
acid-Hb).
• At tissue level, deoxy Hb is available. DeoxyHb can bind much more H than oxy-Hb
(already acidic).
• HCO3 diffuses out into plasma & from plasma,
Cl diffuse in to maintain electrical balance.
This is HCO3-Cl SHIFT OR HAMBERGER’S SHIFT.
• Some CO2 combine with amino group of Hb
to form CARBAMINO-Hb.
• Some CO2 binds with amino group of plasma
proteins to form CARBAMINO-PROTEINS.
Cl
Hb
H
HCO3
carbamino-Hb
H2CO3
CO2 + H20 (CA)
carbamino-proteins
CO2
RBC
B) PHYSICO-CHEMICAL BUFFERING OF
ORGANIC/NON-VOLATILE ACIDS:
• Carried out by various chemical buffers in
body fluids like HCO3 & PO4 buffers.
• e.g in body there is production of H3PO4, so
NaHCO3 will buffer it & we get Na2HPO4 +
H2CO3.
H3PO4 + NaHCO3  Na2HPO4 + H2CO3.
(strong acid)
(salt)
(weak acid)
CONCLUSION:
In case of volatile acids buffering:
Hb & plasma proteins play a role.
Incase of organic/non-volatile acid
buffering:
NaHCO3 is utilized, which must be
replenished & body must get rid of acid
anion/salt & the weak acid; H2CO3.
ROLE OF PHYSIOLOGICAL BUFFERING:
• It is actually to deal with end product of
physico-chemical buffering.
• In physiological buffering, there is role of
respiratory system & renal system.
ROLE OF RESPIRATORY SYSTEM:
• It removes CO2 from the body. Also removes dissolved CO2 (i-e
H2CO3).
• When RBC goes to lung capillaries,
blood becomes oxygenated.
• O2 enters the RBC. O2 binds with Hb to form oxy-Hb (strong
acid), which cannot hold H).
• There is reverse HCO3-Cl shift (lung level).
• From plasma HCO3 move into RBC & Cl move in reverse
direction.
• CO2 from Carbamino Hb also comes out.
• In RBC there is reverse reaction.
H + HCO3  H2CO3  CO2 + H2O.
CO2  alveoli  expired out.
• As a result of physiological buffering, Hb &
plasma proteins are again available to buffer
CO2 or H.
(RECYCLING)
• CO2 is very strong stimulant of respiratory
centre.
• Buffering by respiratory system takes minutes to
hours.
• Buffering power of resp. system is 1 to twice
more powerful, as compared to buffering by
chemical buffers in body fluids (HCO3, PO4
buffers etc).
ROLE OF RENAL SYSTEM:
• Kidneys regenerate HCO3.
• There is reabsorption of Na & Cl ions when
required.
• Acid anions or salts are excreted in urine.
• There is secretion of H & Ammonia by the
kidney.
3) METABOLIC ACIDOSIS:
• Due to increase H ion production in body, conc
of HCO3 decreases. So salt/acid = HCO3/PCO2
= decreased ratio  decreased pH, because of
less HCO3 in arterial blood. So pH decreases
to produce metabolic acidosis.
CAUSES OF METAB ACIDOSIS:
• 1) FAILURE TO EXCRETE normally produced metab
acids in urine. In chronic renal failure, kidneys cannot
excrete normally produced metab acids.
• 2) INCREASED PRODUCTION OF METAB/ORGANIC
ACIDS: e.g uncontrolled DM, Severe hypoxia (lactic
acidosis).
• 3) LOSS OF ALKALINE FLUID FROM BODY:e.g Severe
diarrhoea, intestinal fistula & vomiting of intestinal
contents.
• 4) HYPERKALEMIA: In hyperkalemia, body tends to
excrete K ion, instead of H ion. So H ion is conserved
 acidosis. (IN HYPERKALEMIA THERE IS ACIDOSIS).
• 5) CARBONIC ANHYDRASE INHIBITORS: e.g
Acetazolamide. H ions are not secreted & no reabs of
HCO3  Metabolic acidosis.
COMPENSATION OF MET ACIDOSIS:
• 1) Various buffers in body fluids, buffer the excess of H
ion,e.g, HCO3 buffer, PO4 buffer & protein buffer.
• 2) Resp system: Because of increased H ion conc.
hyperventillation  loss of CO2  less PCO2  Ratio will
increase back to normal & pH will increase back to normal.
• *In compensated cases of metab acidosis, there is some
resp alkalosis to decrease PCO2 because of
hyperventillation.
• 3) Renal compensation: Kidney secretes H ion in large
amount. There is increased NH3 secretion. There is
increased HCO3 reabsorption or regeneration. When there
is more HCO3 reabsorption, Cl is lost in urine.
4) METABOLIC ALKALOSIS:
• There is more HCO3 conc. in arterial blood, so ratio
between salt & acid increases, so pH will increase to
produce metabolic alkalosis.
• CAUSES:
• 1) Ingestion of large amount of alkali ,e.g, in
gastritis & peptic ulcer as a treatment.
• 2) Vomiting of gastric contents, due to loss of acids
from stomach in large amounts.
• 3) Increase of Aldosterone: Increased Na reabs
which is coupled with counter transport of K & also
H, so when there is increased aldosterone 
hypokalemia & alkalosis.
EFFECTS OF ACIDOSIS & ALKALOSIS
ON BODY:
• EFFECT OF ACIDOSIS: When pH decreases 
CNS is depressed  patient becomes
disoriented, drowsy & comatosed in severe
cases, e.g, diabetic coma of ketoacidosis 
Kussmal breathing (rapid & deep breathing)
with ketotic breath.
• EFFECT OF ALKALOSIS: When ionic calcium
decreases  hypocalcemia  tetany
(hyperexcitability of nerves)  carpopedal &
laryngeal spasm, convulsions, paresthesias
due to involvement of sensory nerves.
CLINICAL EVALUATION OF ACID BASE
BALANCE:
-1) MEASUREMENT OF ARTERIAL pH:
(1st parameter) = 7.4
-2) MEASUREMENT OF ARTERIAL PCO2:=
40mmHg
-3) MEASUREMENT OF ALKALI RESERVE: (HCO3)
= 24mEq/L
-4) MEASUREMENT OF BUFFER BASE:
-5) ANION GAP MEASUREMENT:
CLINICAL EVALUATION OF ACID BASE
BALANCE:
• MEASUREMENT OF BUFFER BASE:
• It is conc of anion component of buffers in body
fluid. It includes HCO3 conc & conc of protein anions.
• Normally buffer base is 48mEq/L.
• Out of this, HCO3 is 24 & remaining is Hb (mainly
protein anions).
• We can also evaluate acid base balance by acid base
nomograms. It also determines type of acid base
disturbance & its severity.
• ANION GAP MEASUREMENT: It is the
difference between conc of cations other than
Na & conc of anions other than HCO3 & Cl.
ANION GAP MEASUREMENT:
• [ANIONS] = [CATIONS]
• [MEASURED ANIONS] + [UNMEASURED
ANIONS] = [MEASURED CATIONS] +
[UNMEASURED CATIONS]
• [Cl-] + [HCO3-]
+ [UNMEASURED ANIONS]
=
• [Na+]
+ [UNMEASURED CATIONS]
• [UNMEASURED ANIONS – UNMEASURED
CATIONS =
• [Na+] – [Cl- + HCO3-]
ANIONS OTHER THAN HCO3 & Cl:
• Protein anions, PO4, SO4 & LACTATE.
• Difference between these 2 concs is called
ANION GAP.
• Anion gap is increased, when conc of cations
decreases or anions are increased,e.g,
incresed albumin, SO4,PO4,LACTATE &
PYRUVATE.
ANION GAP IS INCREASED IN:
• Metabolic acidosis due to ketoacidosis & lactacidosis like in
uncontrolled DM (ketoacidosis) & in severe hypoxia
(lactacidosis).
ANION GAP IS NOT INCREASED IN:
• Hyperchloremic acidosis, which may be due to CA Inhibitors
(acetazolamide) or ingestion of large amount of NH4Cl.
1) RESPIRATORY ACIDOSIS:
• Here PCO2 in arterial blood increases, ratio between salt &
acid falls, so pH decreases to produce resp acidosis.
• CAUSES: Decreased rate of pulm vent. due to damage to resp
centre or resp centre depression by drugs like morphine or
disease of resp centre. Resp muscle paralysis, airway
obstruction, pulm fibrosis, pneumothorax & pleural effusion.
• In resp acidosis, cause is in resp system.
• COMPENSATORY MECHANISMS: (from outside
resp system)
• 1) Various non-HCO3 buffers, take up or buffer
H ion to produce HCO3 ion.
When there is increased PCO2, there is more
H2CO3. So non-HCO3 buffers will take up H
ion from H2CO3 & left behind is HCO3.
• 2) Renal compensation:
• In renal tubules, there is more H ion secretion & more NH3
secretion. More HCO3 reabsorption or regeneration. More
titrable acidity of urine.
• As a result of renal compensation, HCO3 will increase.
• Ratio of HCO3/PCO2 conc will increase back to normal  pH
will increase back to normal.
• In compensated cases of resp acidosis, there is some
metabolic alkalosis because HCO3 is increased.
2) RESPIRATORY ALKALOSIS:
• Here PCO2 in arterial blood decreases. So ratio
between salt/acid conc is increased, so pH increases
 resp alkalosis.
CAUSES: Hyper ventilation:
• Voluntary
• Hysteria / psychoneurosis
• Resp centre stimulation in salicylate poisoning &
nikethamide (resp stimulant)
• At high altitude.
• COMPENSATION OF RESP ALKALOSIS:
• 1) By protons donated by various buffers in body
fluids (some compensation).
• 2) Main compensation is through kidneys.
• In kidney, no H ion secretion, no NH3 secretion,
HCO3 is not reabsorbed, it is lost in urine in large
amount. H ions are produced in tubular cells which
are added to ECF. So urine will be highly alkaline.