1. ACID BASE DISORDER
DR WAN NORLINA WAN AZMAN
CHEMICAL PATHOLOGIST
DEPARTMENT OF CHEMICAL PATHOLOGY
SCHOOL OF MEDICAL SCIENCES
UNIVERSITI SAINS MALAYSIA
2. TITLE LOREM IPSUM DOLOR SIT AMET
2017
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2018
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2019
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3. LEARNING OUTCOME
• Acid- base homeostasis concept
• Buffer systems and their role in regulating the pH of body fluids
• Respiratory and renal mechanism in regulation of acid base balance
• Acid base disorder
• Acidosis / Alkalosis
• Metabolic & Respiratory
• Formula and causes of high and normal Anion gap
• Causes of different acid base disturbances
• Understand the concept of compensation in different acid-base disturbances
• Interpret the acid base status base on case example
• Pre-analytical aspect of ABG testing
• Investigation for patient with acid base imbalance
4. ACID BASE HOMEOSTASIS
• Acid: A chemical substance capable of releasing a hydrogen ion (donor of H+).
• Base: Any substance capable of combining with or accepting a hydrogen ion (acceptor
of H+).
• Homeostasis: Maintenance of a constant internal environment.
• Acid-base homeostasis operates to maintain extracellular arterial pH between 7.35- 7.45,
and intracellular pH between 7.0 and 7.3 in order to provide an optimal milieu for
enzymatic and metabolic processes.
5. • The pH of a solution is defined as the negative logarithm of H+ activity (pH= -logaH+)
• Thus, pH is a dimensionless quantity ; a decrease of one pH unit represent 10 fold increase
in the H+ activity
• Potentiometric determinations of blood pH measure H+ activity & not the H+
concentration, although the activity is assumed to equal the concentration.
6. • Bicarbonate is the 2nd largest fraction (behind Cl-) of plasma anions.
• Conventionally it is defined to include : (1) plasma bicarbonate ion, (2)carbonate
and (3)CO2 bound in plasma carbamino compounds.
• Actual bicarbonate ion concentration (cHCO3) is not measured. It is calculated from the
Handerson- Hasselbalch equation.
7.
8. BUFFER SYSTEMS AND THEIR ROLE IN REGULATING
THE PH OF BODY FLUIDS
Buffer systems are systems in which there is a significant (and nearly equivalent) amount of a
weak acid and its conjugate base or vice versa present in solution. This coupling provides a
resistance to change in the solution's pH.
E.g bicarbonate buffer system. If a strong acid is added to solution containing HCO3- &
H2CO3, the H+ will act with HCO3- to form more H2CO3 as well as CO2 and H2O. So H+ will
be minimal. Conversely, if H+ fall, H2CO3 dissociates, so generates more H+.
For every H+ buffered by bicarbonate, a HCO3- is consumed, thus to maintain the capacity of
buffer system, bicarbonate must be regenerated.
9. • Blood buffer systems ; three most important buffers in the blood are :
Bicarbonate system : H2CO3 / HCO3
- (major extracellular buffer in blood)
Protein system : protein+/protein-
Phosphate system : H2PO4 / HPO4
- ; (major buffer in urine)
Others : bone and ammonia
10. RESPIRATORY AND RENAL MECHANISM IN
REGULATION OF ACID BASE BALANCE
• Basically, the regulation of arterial pH includes :
1. Regulation of PaCO2 by the respiratory system.
PaCO2 is regulated by respiration rate, either slowing down or speeding up
respirations, to either blow off or retain CO2. Control comes from the CNS by
regulating respiration rate.
11. • Most metabolic acid base disorders developed slowly, within hours for DKA and months
or even years for CKD.
• The respiratory systems respond immediately to a change in acid base status, but several
hours maybe required for maximal respond. The maximal respond only occurred after
both central & peripheral chemoreceptors are fully stimulated.
12. • E.g ; Early stage of metabolic acidosis, plasma pH decrease but H+ equilibrate rather slowly across BBB,
pH in CSF remain nearly normal. But peripheral chemoreceptor are stimulated by decrease plasma pH
hyperventilation PCO2 decrease. Because of this, PCO2 in CSF decrease immediately (CO2 rapidly
equilibrates in BBB) rise in pH of CSF. This will inhibit central chemoreceptors. But as plasma HCO3
-
gradually fall because of acidosis, pH & HCO3
- will also gradually fall in CSF several hours. At this point
both peripheral & central are maximally stimulated.
•
But reverse happened in patient with metabolic acidosis treated with HCO3
- . Plasma pH will increase with
HCO3
- administration. Stimulation of peripheral chemoreceptor returns to normal. But because of slow
equilibrium of HCO3
- between plasma and CSF, central chemoreceptors continue to be stimulated, patient
will continue to hyperventilate, even when the blood pH become normal. Respiration does not return to
normal until normal acid-base balance in CSF is restored.
13. b. Role of kidney in acid-base homeostasis :
Functions of kidneys respond to different alterations of acid base status. In acidosis
increase excretion of acids & based is conserved ; in alkalosis , the opposite occurs.
This ability to excrete variable amounts of acid or base makes the kidney the final
defense mechanism against changes in body pH.
14. Renal excretion of acid and conservation of HCO3
- occur through several mechanisms ;
• The Na+ -H+ exchange
• Reclamation/reabsorption of filtered HCO3
–
• Production of ammonia and excretion of NH4
+
15. • Na+- H+ exchanger
• In renal tubules ; excrete H+ into the tubular fluid in exchange for Na+ ion.
• Na+- H+ exchange enhanced in states of acidosis & inhibited during alkalotic states.
• H+ of glomerular filtrate, through Na+- H+ exchanger may react with NH3 or
HPO4
2-
• K+ also compete with H+ in renal tubular Na+- H+ exchanger. During hyperkalemia,
more K+ and H+ are exchanged for Na+. As a result, urine become less acidic and
thus lead to acidosis. Whereas hypokalemia lead to alkalosis. Because body’s
compensatory mechanism against metabolic alkalosis is relatively ineffective, K+
depletion alone can result in metabolic alkalosis.
Editor's Notes
dCO2 includes undissociated carbonic acid and free co2
Application of Henderson Hasselbalch equation ; the action of buffers in regulating body pH by using the bicarbonate buffer system;
CO2 and water react to form carbonic acid which later dissociate to H+ and HCO3-
cHCO3 = concentration of bicarbonate
Equation relates to the concentration of acid and base
K’ = combined dissociation constant for carbonic acid
0.0306 = solubility coefficient of CO2 in blood at 37 oC
Phosphate buffer in plasma 5%, and in erythrocytes fluid 16%