3. Introduction
• Acid-base homeostasis critically affects the tissue and organ
performance.
• Both acidosis and alkalosis can have severe and life threatening
consequences.
• It is the nature of the responsible condition that determines the
prognosis.
4. Definitions
• An acid is a substance that can release or donate H+.
• A base is a substance that can combine with or accept H.
• Acid base balance : maintenance of normal pH within the body
systems.
• pH is a logarithmic measure of hydrogen ion concentration.
pH= -log10 [H+]
• Normal body pH : 7.35 - 7.45
• Acidosis < 7.35 alkalosis >7.45
5. Definitions
• The pH of a solution is determined by the pKa or partial acidity
constant and the ratio of the concentration of the conjugate base
to acid.
pH= pKa + log [A-]
[HA]
(Henderson-Hasselbalch equation)
6. Regulation of acid base balance
• The body blood’s pH is strictly regulated between 7.35 – 7.45.
• Minor changes in the body acidity will affect the protein stability
and biochemical process.
• Avoiding acidemia and alkalemia by tightly regulation of H+ is
essential for normal cellular function.
8. Rates of Correction
• Buffers function almost instantaneously
• Respiratory mechanisms take several minutes
to hours
• Renal mechanisms may take several hours to
days
9. Buffering
• The concentration of free hydrogen is controlled by buffers
which acts as hydrogen sponge.
• When [H] is low (high pH) , hydrogen sponges release hydrogen
and increase the free H conc.
• When [H] is high (low pH), hydrogen sponges engulf the free
hydrogen and decrease the free H conc.
• The major Hydrogen buffers are Bicarbonate, inorganic
phosphate and plasma protein.
11. Respiratory Mechanism
• Exhalation of carbon dioxide.
• Powerful, but only works with volatile acids such
as carbonic acid.
• Doesn’t affect fixed acids like lactic acid.
• Body pH can be adjusted by changing rate and
depth of breathing.
12. Respiratory Mechanisms
• Arterial PCO2 stimulates chemorecptors in the medulla
oblongata.
• An elevated arterial blood PCO2 is a stimulus to increase
ventilation leading to increased expiration of CO2 hence
increase blood pH.
• Conversely, a drop in blood PCO2 inhibits ventilation; the
consequent rise in blood [H2CO3] reduces the alkaline shift
in blood pH.
13. Renal regulation
• The role of kidney is to maintain plasma HCO3 concentration and
there by pH regulation.
• The kidneys regulate HCO3 by:
1. Excretion of H ions by tubular secretion.
2. Reabsorption of filtered bicarbonate ions.
3. Production of new HCO3 ions.
14. Mechanism of HCO3
- Reabsorption and
Na+ - H+ Exchange In Proximal Tubule and LOH
19. Anion Gap
• The anion gap is the difference in the
measured cations (positively charged ions)
and the measured anions (negatively charged
ions) in serum or urine.
• It is calculated as :
[Na+] − ([Cl−] + [HCO3−])
• Anion gap is calculated when attempting to
identify the cause of metabolic acidosis.
20. Diagnosis of Acid Base Disorder
1. Determine the primary disturbance:
– Acidemia or Alkalemia: look at the pH
< 7.40 = acidemia
> 7.40 = alkalemia
– Respiratory or Metabolic: look at HCO3 and CO2
HCO3 = primary metabolic acidosis
pCO2 = primary respiratory acidosis
and vice versa for alkalosis
21. Diagnosis of Acid Base Disorder
2. Primary Metabolic Disturbance:
o Calculate anion gap : Na – (Cl + HCO3)
o Normal = 12 +/- 2
o If gap is >20 then there is primary metabolic acidosis regardless of
pH or bicarb.
o Helps narrow differential with a anion gap or non- anion gap metabolic
acidosis
22. Diagnosis of Acid Base Disorder
4. Assess appropriate respiratory compensation
for metabolic disorder:
o Respiratory compensation is fast
o Winters formula:
Expected pCO2 = (1.5 * HCO3) + 8 (+/-2)
o If measured pCO2 is
< expected then co-existing resp. alkalosis
> expected then co-existing resp. acidosis
23. Clinical correlation: Example 1
• A 15 year old boy is brought from examination hall in apprehensive
state with complain of tightness of chest.
pH 7.54 HCO3 21 mEq/L PaCO2 21 mm of hg
24. Example 1 : Analysis
• pH is high so patient has alkalosis.
• Low PaCo2 is suggestive of respiratory alkalosis.
• HCO3 is also low suggestive of compensation (follows same direction
rule)
• Expected acute compensation (fall in HCO3) in respiratory alkalosis.
• So the patient has primary respiratory alkalosis due to anxiety.
25. Example 2
• A patient with poorly controlled IDDM missed his insulin for 3 days.
pH 7.1
mEq/l
HCO3 8 mEq/l PaCO2 20 mmhg Na 140
CL 106 mEq/l and urinary ketones +++
26. Example 2: Analysis
• pH is low so patient has acidosis. Low HCO3 is suggestive of
metabolic acidosis. PaCO2 is also low suggestive of compensation.
• AG is 26 (AG=Na-(Cl+HCO3)=140-(106+8)=140-114=26, which is high.
• So high AG Metabolic Acidosis. Presence of urinary ketones suggests
presence of diabetic ketoacidosis.
• So the patient has high anion gap metabolic acidosis due to DKA
27. Example 3
• A patient with severe diarrhea, c/o difficulty in breathing (due to
muscle weakness).
pH 7.1 HCO3 14 mEq/l PaCO2 44 mmhg K 2.0 mEq/l
28. Example 3: Analysis
• pH is low so patient has acidosis.
• Low HCO3 is sign of metabolic acidosis.
• PaCO2 is expected to reduce due to compensation. However actual
PaCO2 is high, which is indicates presence of associated respiratory
acidosis.
• Very low K causing weakness of respiratory muscles is the cause of
respiratory failure leading to respiratory acidosis. So this patient has
mixed disorder ,metabolic acidosis with respiratory acidosis.
This process occurs in the proximal convoluted tubules.
The CO2 combines with water to form carbonic acid, with the help of carbonic anhydrase.
The H2CO3 then ionizes to H+ and bicarbonate. The hydrogen ions are secreted into the tubular lumen; in exchange for Na+ reabsorbed. These Na+ along with HCO3- will be reabsorbed into the blood.
There is net excretion of hydrogen ions, and net generation of bicarbonate.
This mechanism serves to increase the alkali reserve.
H+ is secreted via a Na-H counter-transport process, coupled to the active movement of Na+ into the interstitial fluid via the basolateral Na-K ATPase.
Similar process occur in distal and collecting tubules