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Acid – Base Balance
• Acid-base balance is very important for the
homeostasis of the body and almost all the
physiological activities depend upon the acid-
base status of the body.
• Acids are constantly produced in the body.
• However, the acid production is balanced by
the production of bases so that the acid-base
status of the body is maintained.
Some Definitions:
• Acid: is any proton donor (a molecule that releases a
proton H+ in water).
A. Strong acids: HCL.
B. Weak acids: Carbonic acid (H2CO3), Lactic acids and
sodium dihydrogen phosphate (NaH2PO4).
• Base: is a proton acceptor (a substance accept H+
often with the release of hydroxyl (OH-) ions).
A. Strong base: Hydroxyl ion (OH-).
B. Weak base: Bicarbonate (HCO3).
• In practice, the acidotic conditions are common
than alkalotic ones, because the body tends to
produce more acid than alkali.
HYDROGEN ION AND pH:
• Hydrogen ion (H+) contains only a single
proton (positively charged particle).
• It is the smallest ionic particle, it is highly
reactive.
• The normal H+ concentration in the
extracellular fluid (ECF) is 38 to 42 nM/L.
• The pH is another term for H+ concentration
that is generally used nowadays instead of
‘hydrogen ion concentration’.
• An increase in H+ ion concentration decreases
the pH (acidosis) and a reduction in H+
concentration increases the pH (alkalosis).
• In a healthy person, the pH of the ECF is 7.40 and
it varies between 7.38 and 7.42.
• The maintenance of acid-base status is very
important for homeostasis, because even a slight
change in pH below 7.38 or above 7.42 will cause
serious threats to many physiological functions.
REGULATION OF ACID-BASE
BALANCE:
• Two types of acids are produced in the body:
1. Volatile acids.
2. Non-volatile acids.
1. Volatile Acids:
• Volatile acids are derived from CO2.
• Large quantity of CO2 is produced during the metabolism of carbohydrates and
lipids.
• This CO2 is not a threat because it is almost totally removed through expired air
by lungs.
2. Non-volatile Acids:
• Non-volatile acids are produced during the metabolism of other nutritive
substances such as proteins.
• These acids are real threat to the acid-base status of the body.
• For example, sulfuric acid is produced during the metabolism of sulfur
containing amino acids such as cysteine and metheonine; hydrochloric acid is
produced during the metabolism of lysine, arginine and histidine.
• Fortunately, body is provided with the best regulatory mechanisms to prevent
the hazards of acid production.
Compensatory Mechanism:
• The body has three different mechanisms to regulate acid-base
status:
1. Acid-base buffer system, which binds free H+
2. Respiratory mechanism, which eliminates CO2
3. Renal mechanism, which excretes H+ and conserves the bases
(HCO3–).
• Among the three mechanisms, the acid-base buffer system is
the fastest one and it read justs the pH within seconds.
• The respiratory mechanism does it in minutes.
• Whereas, the renal mechanism is slower and it takes few hours
to few days to bring the pH back to normal.
• However, the renal mechanism is the most powerful mechanism
than the other two in maintaining the acid-base balance of the
body fluids.
1- REGULATION OF ACID-BASE BALANCE
BY ACID-BASE BUFFER SYSTEM:
• An acid-base buffer system is the combination
of a weak acid (protonated substance) and a
base – the salt (unprotonated substance).
• Types of Buffer Systems:
1. Bicarbonate buffer system.
2. Phosphate buffer system.
3. Protein buffer system.
Bicarbonate Buffer System:
• Bicarbonate buffer system is present in ECF (plasma).
• HCO3 – is in the form of salt, i.e. sodium bicarbonate
(NaHCO3).
• Mechanism of action of bicarbonate buffer system:
• HCl + NaHCO3. this action activated when (fall of pH).
• (NaOH) + H2CO3. this action activated when (rise of pH).
• Importance of bicarbonate buffer system:
• Concentration of HCO3 – is regulated by kidney and the
concentration of CO2 is regulated by the respiratory
system.
Phosphate Buffer System:
• Phosphate buffer system is useful in the intracellular fluid
(ICF), in red blood cells or other cells, as the concentration
of phosphate is more in ICF than in ECF.
• Mechanism of phosphate buffer system:
• HCl + Na2HPO4.
• NaOH + NaH2PO4.
• Importance of phosphate buffer system:
• phosphate buffer is useful in tubular fluids of kidneys.
• The elements of phosphate buffer inside the red blood
cells are in the form of potassium dihydrogen phosphate
(KH2PO4) and dipotassium hydrogen phosphate (K2HPO4).
Protein Buffer System:
• Protein buffer systems are present in the blood; both in
the plasma and erythrocytes.
• Protein buffer systems in plasma:
i. C-terminal carboxyl group, N-terminal amino group and
side-chain carboxyl group of glutamic acid.
ii. Side-chain amino group of lysine
iii. Imidazole group of histidine.
• Protein buffer system in erythrocytes (Hemoglobin):
• Hemoglobin has about six times more buffering capacity
than the plasma proteins.
• When a hemoglobin molecule becomes deoxygenated in
the capillaries, it easily binds with H+, which are released
when CO2 enters the capillaries.
2- REGULATION OF ACID-BASE
BALANCE BY RESPIRATORY
MECHANISM:
• CO2 + H2O → H2CO3 → H+ + HCO3 –.
• Entire reaction is reversed in lungs when CO2
diffuses from blood into the alveoli of lungs.
• When metabolic activities increase, more amount of
CO2 is produced in the tissues and the concentration
of H+ increases as seen above.
• Increased H+ concentration increases the pulmonary
ventilation (hyperventilation) by acting through the
chemoreceptors.
• Due to hyperventilation, the excess of CO2 is
removed from the body.
3- REGULATION OF ACID-BASE BALANCE BY
RENAL MECHANISM:
• Kidney maintains the
acid-base balance of
the body by the
secretion of H+ and
by the retention of
HCO3–.
DISTURBANCES
OF ACID-BASE
STATUS
• ACIDOSIS:
• Acidosis is the reduction in pH (increase in H+
concentration) below normal range.
• Acidosis is produced by:
1. Increase in partial pressure of CO2 in the body fluids
particularly in arterial blood
2. Decrease in HCO3– concentration.
• ALKALOSIS:
• Alkalosis is the increase in pH (decrease in H+
concentration) above the normal range.
• Alkalosis is produced by:
1. Decrease in partial pressure of CO2 in the arterial blood
2. Increase in HCO3 – concentration.
• Since the partial pressure of CO2 (pCO2) in arterial
blood is controlled by lungs, the acid-base
disturbances produced by the change in arterial
pCO2 are called the respiratory disturbances.
• On the other hand, the disturbances in acid-base
status produced by the change in HCO3 –
concentration are generally called the metabolic
disturbances.
• Thus the acid-base disturbances are:
1. Respiratory acidosis
2. Respiratory alkalosis
3. Metabolic acidosis
4. Metabolic alkalosis.
RESPIRATORY ACIDOSIS:
• Respiratory acidosis is the acidosis that is caused by
alveolar hypoventilation.
• During hypoventilation the lungs fail to expel CO2.
• CO2 accumulates in blood where it reacts with
water to form carbonic acid, which is called
respiratory acid.
• Carbonic acid dissociates into H+ and HCO3 –.
• The increased H+ concentration in blood leads to
decrease in pH and acidosis.
• Normal partial pressure of CO2 in arterial blood is
about 40 mm Hg. When it increases above 60 mm
Hg acidosis occurs.
Causes of Excess CO2 in the
Body:
• Hypoventilation (decreased ventilation) is the
primary cause for excess CO2 in the body.
RESPIRATORY ALKALOSIS:
• Respiratory alkalosis is the alkalosis that is caused
by alveolar hyperventilation.
• Hyperventilation causes excess loss of CO2 from
the body.
• Loss of CO2 leads to decreased formation of
carbonic acid and decreased release of H+.
• Decreased H+ concentration increases the pH
leading to respiratory alkalosis.
• When the partial pressure of CO2 in arterial
blood decreases below 20 mm Hg, alkalosis
occurs.
Causes of Decrease in CO2 in
the Body:
• Hyperventilation is primary cause for loss of
excess CO2 from the body.
METABOLIC ACIDOSIS:
• Metabolic acidosis is the acid-base imbalance
characterized by excess accumulation of
organic acids in the body, which is caused by
abnormal metabolic processes.
• Organic acids such as lactic acid, ketoacids
and uric acid are formed by normal
metabolism.
• The quantity of these acids increases due to
abnormality in the metabolism.
Causes of Metabolic Acidosis:
METABOLIC ALKALOSIS:
• Metabolic alkalosis is the acid-base imbalance
caused by loss of excess H+ resulting in
increased HCO3– concentration.
• Some of the endocrine disorders, renal
tubular disorders, etc. cause metabolic
disorders leading to loss of H+.
• It increases HCO3 – and pH in the body
leading to metabolic alkalosis.
Causes of Metabolic Alkalosis:
CLINICAL EVALUATION OF DISTURBANCES IN
ACID-BASE STATUS – ANION GAP
• Anion gap is an important measure in the clinical
evaluation of disturbances in acid-base status.
• Only few cations and anions are measured during routine
clinical investigations.
• Commonly measured cation is sodium and the
unmeasured cations are potassium, calcium and
magnesium.
• Usually measured anions are chloride and bicarbonate.
• The unmeasured anions are phosphate, sulfate, proteins
in anionic form such as albumin and other organic anions
like lactate.
• Difference between concentrations of unmeasured anions
and unmeasured cations is called anion gap.
• It is calculated as:
• Normal value of anion gap is 9 to 15 mEq/L.
• It increases when concentration of unmeasured
anion increases and decreases when concentration
of unmeasured cations decreases.
• Anion gap is a useful measure in the differential
diagnosis (diagnosis of the different causes) of
acid - base disorders particularly the metabolic
acidosis.
Lecture 7 (acid base balance)

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Lecture 7 (acid base balance)

  • 1. Acid – Base Balance
  • 2.
  • 3. • Acid-base balance is very important for the homeostasis of the body and almost all the physiological activities depend upon the acid- base status of the body. • Acids are constantly produced in the body. • However, the acid production is balanced by the production of bases so that the acid-base status of the body is maintained.
  • 4. Some Definitions: • Acid: is any proton donor (a molecule that releases a proton H+ in water). A. Strong acids: HCL. B. Weak acids: Carbonic acid (H2CO3), Lactic acids and sodium dihydrogen phosphate (NaH2PO4). • Base: is a proton acceptor (a substance accept H+ often with the release of hydroxyl (OH-) ions). A. Strong base: Hydroxyl ion (OH-). B. Weak base: Bicarbonate (HCO3). • In practice, the acidotic conditions are common than alkalotic ones, because the body tends to produce more acid than alkali.
  • 5.
  • 6. HYDROGEN ION AND pH: • Hydrogen ion (H+) contains only a single proton (positively charged particle). • It is the smallest ionic particle, it is highly reactive. • The normal H+ concentration in the extracellular fluid (ECF) is 38 to 42 nM/L. • The pH is another term for H+ concentration that is generally used nowadays instead of ‘hydrogen ion concentration’.
  • 7.
  • 8. • An increase in H+ ion concentration decreases the pH (acidosis) and a reduction in H+ concentration increases the pH (alkalosis). • In a healthy person, the pH of the ECF is 7.40 and it varies between 7.38 and 7.42. • The maintenance of acid-base status is very important for homeostasis, because even a slight change in pH below 7.38 or above 7.42 will cause serious threats to many physiological functions.
  • 9. REGULATION OF ACID-BASE BALANCE: • Two types of acids are produced in the body: 1. Volatile acids. 2. Non-volatile acids. 1. Volatile Acids: • Volatile acids are derived from CO2. • Large quantity of CO2 is produced during the metabolism of carbohydrates and lipids. • This CO2 is not a threat because it is almost totally removed through expired air by lungs. 2. Non-volatile Acids: • Non-volatile acids are produced during the metabolism of other nutritive substances such as proteins. • These acids are real threat to the acid-base status of the body. • For example, sulfuric acid is produced during the metabolism of sulfur containing amino acids such as cysteine and metheonine; hydrochloric acid is produced during the metabolism of lysine, arginine and histidine. • Fortunately, body is provided with the best regulatory mechanisms to prevent the hazards of acid production.
  • 10. Compensatory Mechanism: • The body has three different mechanisms to regulate acid-base status: 1. Acid-base buffer system, which binds free H+ 2. Respiratory mechanism, which eliminates CO2 3. Renal mechanism, which excretes H+ and conserves the bases (HCO3–). • Among the three mechanisms, the acid-base buffer system is the fastest one and it read justs the pH within seconds. • The respiratory mechanism does it in minutes. • Whereas, the renal mechanism is slower and it takes few hours to few days to bring the pH back to normal. • However, the renal mechanism is the most powerful mechanism than the other two in maintaining the acid-base balance of the body fluids.
  • 11.
  • 12. 1- REGULATION OF ACID-BASE BALANCE BY ACID-BASE BUFFER SYSTEM: • An acid-base buffer system is the combination of a weak acid (protonated substance) and a base – the salt (unprotonated substance). • Types of Buffer Systems: 1. Bicarbonate buffer system. 2. Phosphate buffer system. 3. Protein buffer system.
  • 13. Bicarbonate Buffer System: • Bicarbonate buffer system is present in ECF (plasma). • HCO3 – is in the form of salt, i.e. sodium bicarbonate (NaHCO3). • Mechanism of action of bicarbonate buffer system: • HCl + NaHCO3. this action activated when (fall of pH). • (NaOH) + H2CO3. this action activated when (rise of pH). • Importance of bicarbonate buffer system: • Concentration of HCO3 – is regulated by kidney and the concentration of CO2 is regulated by the respiratory system.
  • 14.
  • 15. Phosphate Buffer System: • Phosphate buffer system is useful in the intracellular fluid (ICF), in red blood cells or other cells, as the concentration of phosphate is more in ICF than in ECF. • Mechanism of phosphate buffer system: • HCl + Na2HPO4. • NaOH + NaH2PO4. • Importance of phosphate buffer system: • phosphate buffer is useful in tubular fluids of kidneys. • The elements of phosphate buffer inside the red blood cells are in the form of potassium dihydrogen phosphate (KH2PO4) and dipotassium hydrogen phosphate (K2HPO4).
  • 16.
  • 17. Protein Buffer System: • Protein buffer systems are present in the blood; both in the plasma and erythrocytes. • Protein buffer systems in plasma: i. C-terminal carboxyl group, N-terminal amino group and side-chain carboxyl group of glutamic acid. ii. Side-chain amino group of lysine iii. Imidazole group of histidine. • Protein buffer system in erythrocytes (Hemoglobin): • Hemoglobin has about six times more buffering capacity than the plasma proteins. • When a hemoglobin molecule becomes deoxygenated in the capillaries, it easily binds with H+, which are released when CO2 enters the capillaries.
  • 18.
  • 19. 2- REGULATION OF ACID-BASE BALANCE BY RESPIRATORY MECHANISM: • CO2 + H2O → H2CO3 → H+ + HCO3 –. • Entire reaction is reversed in lungs when CO2 diffuses from blood into the alveoli of lungs. • When metabolic activities increase, more amount of CO2 is produced in the tissues and the concentration of H+ increases as seen above. • Increased H+ concentration increases the pulmonary ventilation (hyperventilation) by acting through the chemoreceptors. • Due to hyperventilation, the excess of CO2 is removed from the body.
  • 20.
  • 21. 3- REGULATION OF ACID-BASE BALANCE BY RENAL MECHANISM: • Kidney maintains the acid-base balance of the body by the secretion of H+ and by the retention of HCO3–.
  • 23.
  • 24. • ACIDOSIS: • Acidosis is the reduction in pH (increase in H+ concentration) below normal range. • Acidosis is produced by: 1. Increase in partial pressure of CO2 in the body fluids particularly in arterial blood 2. Decrease in HCO3– concentration. • ALKALOSIS: • Alkalosis is the increase in pH (decrease in H+ concentration) above the normal range. • Alkalosis is produced by: 1. Decrease in partial pressure of CO2 in the arterial blood 2. Increase in HCO3 – concentration.
  • 25. • Since the partial pressure of CO2 (pCO2) in arterial blood is controlled by lungs, the acid-base disturbances produced by the change in arterial pCO2 are called the respiratory disturbances. • On the other hand, the disturbances in acid-base status produced by the change in HCO3 – concentration are generally called the metabolic disturbances. • Thus the acid-base disturbances are: 1. Respiratory acidosis 2. Respiratory alkalosis 3. Metabolic acidosis 4. Metabolic alkalosis.
  • 26. RESPIRATORY ACIDOSIS: • Respiratory acidosis is the acidosis that is caused by alveolar hypoventilation. • During hypoventilation the lungs fail to expel CO2. • CO2 accumulates in blood where it reacts with water to form carbonic acid, which is called respiratory acid. • Carbonic acid dissociates into H+ and HCO3 –. • The increased H+ concentration in blood leads to decrease in pH and acidosis. • Normal partial pressure of CO2 in arterial blood is about 40 mm Hg. When it increases above 60 mm Hg acidosis occurs.
  • 27. Causes of Excess CO2 in the Body: • Hypoventilation (decreased ventilation) is the primary cause for excess CO2 in the body.
  • 28.
  • 29. RESPIRATORY ALKALOSIS: • Respiratory alkalosis is the alkalosis that is caused by alveolar hyperventilation. • Hyperventilation causes excess loss of CO2 from the body. • Loss of CO2 leads to decreased formation of carbonic acid and decreased release of H+. • Decreased H+ concentration increases the pH leading to respiratory alkalosis. • When the partial pressure of CO2 in arterial blood decreases below 20 mm Hg, alkalosis occurs.
  • 30. Causes of Decrease in CO2 in the Body: • Hyperventilation is primary cause for loss of excess CO2 from the body.
  • 31.
  • 32. METABOLIC ACIDOSIS: • Metabolic acidosis is the acid-base imbalance characterized by excess accumulation of organic acids in the body, which is caused by abnormal metabolic processes. • Organic acids such as lactic acid, ketoacids and uric acid are formed by normal metabolism. • The quantity of these acids increases due to abnormality in the metabolism.
  • 33. Causes of Metabolic Acidosis:
  • 34.
  • 35. METABOLIC ALKALOSIS: • Metabolic alkalosis is the acid-base imbalance caused by loss of excess H+ resulting in increased HCO3– concentration. • Some of the endocrine disorders, renal tubular disorders, etc. cause metabolic disorders leading to loss of H+. • It increases HCO3 – and pH in the body leading to metabolic alkalosis.
  • 36. Causes of Metabolic Alkalosis:
  • 37.
  • 38. CLINICAL EVALUATION OF DISTURBANCES IN ACID-BASE STATUS – ANION GAP • Anion gap is an important measure in the clinical evaluation of disturbances in acid-base status. • Only few cations and anions are measured during routine clinical investigations. • Commonly measured cation is sodium and the unmeasured cations are potassium, calcium and magnesium. • Usually measured anions are chloride and bicarbonate. • The unmeasured anions are phosphate, sulfate, proteins in anionic form such as albumin and other organic anions like lactate. • Difference between concentrations of unmeasured anions and unmeasured cations is called anion gap.
  • 39. • It is calculated as: • Normal value of anion gap is 9 to 15 mEq/L. • It increases when concentration of unmeasured anion increases and decreases when concentration of unmeasured cations decreases. • Anion gap is a useful measure in the differential diagnosis (diagnosis of the different causes) of acid - base disorders particularly the metabolic acidosis.