acid base homeostasis

1. ACID BASE
HOMEOSTASIS
BY
DR KABIRU ABDULSALAM
MBBS(BUK), FWACP(Lab Med)
LECTURER/CONSULTANT CHEMICAL PATHOLOGIST
BUK/AKTH

2. Outline
 Learning Objectives
 Introduction
 Important concepts
 Henderson Hasselbalch equation
 Acid base Homeostasis
 The bicarbonate buffer system
 Blood Buffer system
 GI and Acid base homeostasis
 Urinary buffer system
 Blood Gases
 Laboratory evaluation of Acid Base status
 Conclusion

3. Objectives
 Revise the basic concepts of acid base homeostasis.
 Understand the role of the Kidney, lungs and the
gastro intestinal tracts in acid base homeostasis
and also pathologic basis of various abnormalities.
 Discuss the various blood and urinary buffers and
their control systems.
 Elucidate the basis of laboratory evaluation of
patients with acid base disorders.
 Develop critical thinking required in the rational use
of the chemical pathology laboratory in evaluating
patients suspected to have Acid Base
abnormalities.

4. Important
concepts
 Acids are substances that can dissociate to produce
proton that can be accepted by a base
 Classification and examples of acids
 Alkali or a base dissociates to produce OH‾
 Buffering is a process by which a strong acid is
replaced by a weak one resulting in reduction in the
number of free H+
 pH is a measure of H+ it is defined as negative log
of [H+]
 Optimum pH for biological reactions which are
mainly enzyme catalysed is 7.35-7.45
 pH must therefore be maintained within this
narrow range

5. Henderson
Hasselbalch
equation
 Expresses the relation between pH and a buffer pair
 Derivation of the HH equation
 pH= Pka + log [Base]/[Acid]
 For the most important buffer system in the body
 pH= pKa + log[HCO‾₃]/S. PCO₂
 S= solubility coefficient of CO₂= 0.23 or 0.03
depending on the unit of measurement of the PCO₂
 Pka for the bicarbonate buffer system = 6.1

6. Sources of
H+ andCO₂
 Hydrogen ions are derived from the several
biochemical reactions that take place in the body
such as
 Anaerobic metabolism of carbohydrates producing
lactate
 Catabolism of Ketogenic amino acids producing
acetoacetate
 Metabolism of fatty acids through β – oxidation to
produce acetyl Co-A
 Conversion ofAmino nitrogen to urea
 Conversion of SH groups in Cysteine and
Methionine to sulphate
 Carbon(IV) oxide is generated by the aerobic
metabolism of carbon skeleton in CHO, amino acids
and Fatty acids
 There is more tendency to acidosis than alkalosis

7. Acid base
control
systems
 50-100 mmol of H+ are produced in 24Hrs
 The body maintain [H+] at about 40nmol/L
 The primary organs of acid base homeostasis are
the Kidneys and the Lungs
 Systems are aimed at immediate buffering and
ultimately elimination of excess H+ and CO₂ from
the body
 Plasma [HCO3] is controlled mainly by the kidney
 PCO₂ is controlled mainly by the lungs
 Metabolic abnormalities are corrected by adjusting
the respiratory system and compensation is usually
immediate but incomplete
 Respiratory disorders are corrected by adjusting
the renal system

8. Bicarbonate
Buffer
system
 This is the most important buffer system of the ECF
compartment
 pKa = 6.1
 Ability to generate large quantities of bicarbonate
 It linked the Plasma, pulmonary and Urinary
systems as well the Gastrointestinal system.
 It is necessary for efficient buffering by the Hb in
RBCs
 Buffering is a temporary measure and the H+ must
be removed or eliminated from the body
 H+ can be removed from the body only through the
Kidney and the GIT

10. Acid base
control
mechanisms:
Lungs
 CO₂ and H+ are potentially toxic metabolic products that
must be removed from the biological system
 Carbon (IV) oxide is mainly eliminated by the lungs, a small
but significant quantity is converted to HCO₃ by RTCs and
RBCs
 Oxygen is transported to the tissues by Hb in the RBCs where
it is oxidized to CO₂
 The CO₂ diffuse out of the tissues into ECF and eventually
into the alveolar spaces from where it is exhaled out.
 The rate of elimination of the CO₂ is controlled by
chemoreceptors in the brain stem, carotid and aortic bodies
 These receptors are sensitive to changes in [H+] and [CO₂]
 Aimed at maintaining PCO₂ around 5.3 Kpa
 Rate of respiration can increase or decrease to maintain the
above
 There is a very large capacity for eliminating CO₂ by the lungs

11. Carbonic
Anhydrase
system(CD)
 An important enzyme present mainly in the RTCs,
RBC and certain ophthalmic cells that plays key role in
maintaining intraocular pressure
 The CD present mainly in the RBC and RTC perform a
very important function of maintaining the acid base
homeostasis
 CO₂+ H₂O ↔ H₂CO3 ↔ H+ +HCO₃
 Bicarbonate generation is therefore enhanced in:
 Rise in CO₂
 Fall in HCO₃
 Fall in H+ because it is buffered by Hb or excreted by
the body through the kidneys.
 Normal subjects: pCO₂ =5.3 Kpa, [HCO₃] =25 mmol/L
 ECF [HCO₃]/[CO₂] approx 20:1 and a pKa of 6.1
 Represent a pH of about 7.4

12. The Role of
RBC
 Only anaerobic metabolism
 Ample quantity of CD
 Presence of water
 CO₂ diffuses freely through the red cell membrane
 H+ is buffered by the Hb and bicarbonate diffuses
out
 Electrochemical neutrality is maintained by
chloride shift.
 Other Blood buffers: plasma proteins and
Phosphate buffers
 Both limited by low concentration in the plasma

14. The role of
the Kidney
 The kidneys performs several metabolic functions
 Regulation of the internal milieu
 Water, sodium, potassium and acid base
homeostasis
 Elimination/excretion of H+ ions
 RTC have abundant quantity of CD
 Maintains optimum conc of bicarbonate in the ECF
 Bicarbonate reclamation and Bicarbonate
generation

15. HCO₃
Reclamation
 An important process of maintaining the steady
state
 All the filtered bicarbonate is reclaimed or
reabsorbed through an elaborate process
 No net loss of H+
 The CD reaction in the lumen is derived from
filtered bicarbonate
 The process can not correct for acidosis

17. Bicarbonate
reclamation:
the steps
 Glomerular filterate contain bicarbonate at about
25 mmol/L and Na at about 140mmol/L
 Na is exchanged for H+
 HCO3 combine with the H+ to form carbonic acid
 Carbonic acid dissociates to water and Carbon IV
oxide
 The CO2 diffuses into the RTC where it combine
with water to form carbonic acid in a reaction also
catalysed by CD
 Carbonic acid dissociates to Bicarbonate and H+
and the cycle is repeated

18. Bicarbonate
generation
 The process is similar to that of bicarbonate
reclamation.
 They all depend on CD catalysed reactions
 The CO2 in this reaction is derived from cellular
reactions within the RTC
 The process become more prominent after all the
filtered bicarbonate is reclaimed
 There is net generation of Bicarbonate and
excretion/elimination of H+
 Continued elimination of H+ depend on the
presence of filtered buffer bases
 Can be stimulated by a fall in ECF bicarbonate level
or a rise in ECF PCO₂
 Constitute an important mechanism for correcting
acidosis

19. The
Phosphate
buffer pair
 At pH lower than 7.4 Continued elimination of H+
and generation of HCO₃ is hinged on the availability
of other buffers mainly the Phosphate buffer
system and Ammonia system
 It has a pKa of 6.8
 pH = 6.8 + log [HPO₄]/[H₂PO₄]-
 Conc of Phosphate can increase to 20x
 More phosphate can be mobilized from the bony
skeleton
 Becomes less important as the pH of the luminal
fluid falls below 5.5 as almost all the phosphate is in
the form of H₂PO₄

21. Ammonia
Buffer
system
 At luminal fluid pH lower than 5.5 the buffering
capacity of the other systems are exhausted
 Continued elimination of H+ and production of
bicarbonate depends on availability of NH₃
 The ammonia is derived from catabolism of
Glutamine to Glutamate
 The ammonia reacts with H+ and Cl in the luminal
fluid to form NH₄Cl which is excreted
 Glutamate is further deaminated to 2-oxoglutarate
which is eventually channelled in to
gluconeogenesis and driving the reaction to the
right.

23. TheGIT and
Acid base
Homeostasis
 The function of the GI is intricately connected to
the CD enzyme
 Ability of the gastric parietal cells to produce HCl,
that of the pancreatic and biliary cells to produce
NaHCO₃ to neutralize the acid and also the ability
of the ileal and colonic mucosa to absorb Cl- largely
depends on the CD catalysed reaction.
 The system however has little contribution
physiologically in maintaining acid base
homeostasis

24. Summary

25. Disorders of
acid base
balance

26. Thank You Very
Much for your Kind
Attention