The document discusses acid-base homeostasis and disorders, describing how the body maintains pH between 7.35-7.45 through buffer systems like bicarbonate that are regulated by respiration and the kidneys; it examines types of acid-base imbalances like metabolic acidosis and alkalosis, their causes, features, and treatment; and covers respiratory acidosis which results from excess carbon dioxide due to hypoventilation.

1. Acid base Homeostasis and
disorders
Dr Zainab Yaseen

3. • p H is the negative logarithm of hydrogen ion
concentration
• Normal p H of plasma is 7.35-7.45 (7.4±0.05)
• It is strictly maintained within these limits.
• Any disturbances in plasma pH is considered to be a
medical emergency.
• A decrease in p H ie p H < 7.35 is called acidosis
• An increase in p H ie p H > 7.45 is called alkalosis

4. Buffers
• Buffer: A buffer is a combination of weak acid
and its salt from a strong base or weak base
and its salt.
• A buffer resists changes in p H.
• The effectiveness of a buffer depends on
• pKa of the buffering system and
• The environment in which it is placed

5. An Example
CH3COOH + CH3COONa buffer
• If H+ is added CH3COONa dissociates to
CH3COO- and Na+
• CH3COO combines with H+ to form CH3COOH
On the other hand
• If NaOH is added to the buffer, CH3COOH
dissociates to CH3COO- and H+
• CH3COO- combines with Na to form
CH3COONa and H+ with OH to form H2O

6. How do buffers act
• Buffers can neither remove hydrogen ions from the
body nor add them to it.
• They can only keep the hydrogen ions in suspended
forms to be removed ultimately by kidneys or lungs.
There are 3 major buffer systems in our body:
1. Bicarbonate buffer
2. Phosphate buffer
3. Protein buffer

7. Henderson Hasselbalch equation
• It is an equation showing relationship between
p H , dissociation constant p K and the ratio of
base( salt) to acid of a buffer solution.

8. Major buffers systems in body
EXTRACELLULAR
COMPARTMENT
INTRACELLULAR
COMPARTMENT
RBC URINE
NaHCO3/H2CO3 buffer
also called bicarbonate
buffer
Major buffer
KHCO3/H2CO3 KHCO3/H2CO3 NH3 generated from
glutamine
Na2HPO4/NaH2PO4
Phosphate buffer
Minor buffer
K2HPO4/KH2PO4
Major buffer in
intracellular fluids
K2HPO4/KH2PO4 Na2HPO4/NaH2PO4
Phosphate buffer
Responsible for
titrable acidity in
urine
Na Albumin/albuminH K protein/proteinH K Hb/HbH
Hemoglobin buffer
Major buffer
--

9. Bicarbonate buffer
• It is the main buffer present in extracellular
fluids and plasma.
• It accounts for 65% of buffering capacity of
plasma.
• This is the only buffer regulated by two major
systems in our body
• The base of the pair (HCO3) is regulated by the
kidneys

10. Bicarbonate buffer
• The acid part ( H2CO3) is regulated by the
respiratory system.
• The concentration of HCO3 in plasma is 22-26
mmol/L, mean 24 mmol/L
• Normal p CO2 level in plasma is around 40 mm
of Hg.
• The solubility constant to CO2 is 0.030.

11. • The p Ka of H2CO3 ( dissociation constant) is
6.1.
• Substituting the values in Henderson
Hasselbalch equation:

13. Bicarbonate Buffer
• In bicarbonate buffer the of base(salt) to acid ratio is
20:1
• This shows that bicarbonate buffer has high alkali
reserve.
• The bicarbonate reserve in our body is 20 times the
carbonic acid produced.
• When the blood p H falls the H+ ions combines with
HCO3 to form H2CO3 which dissociates into C02 and
H20
• C02 is excreted through lungs.
• C02 is a major stimulator of respiratory centre in brain.
• It increases the rate and depth of respiration.

14. • On the other hand when HCO3- levels increase
leading to increase in blood pH,
Kidney excretes more of alkaline urine to
restore the blood p H.
Thus bicarbonate buffer has renal and respiratory
regulation.
The major acid base disorders are related to
bicarbonate buffer

15. Phosphate buffer
• Major intracellular buffer.
• Major urinary buffer
• In plasma it has only 5% buffering action
• Consist of Na2HPO4 and NaH2PO4
• The p Ka of the buffer system is 6.8
• The ratio of base/acid is 4:1.

17. • Phosphate buffer is responsible for the titrable
acidity of urine
• It is regulated by the kidneys.

18. Protein buffers
• The buffering actions of proteins depend on
their amino acid composition.
• The imidazole group of histidine is mainly
responsible for the buffering action of proteins.
• The p Ka of imidazole group is 6.1 which is close
to blood p H.
• Albumin has 16 histidine residues. Hence it is
the major buffering protein in plasma.

19. Hemoglobin buffer
• Hemoglobin is a major buffer inside RBC.
• The imidazole group of histidine is responsible
for the buffering actions of Hemoglobin.

20. Regulation of blood p H

21. Respiratory Regulation
• The respiratory system and the kidneys
together maintain the body p H
• The respiratory response to changes in pH is
swift and occurs within minutes
• The response of the kidneys is slow and steady
and takes hours to days
• The respiratory system regulates the levels of
carbonic acid in blood

22. Role of respiratory centre
• The chemoreceptors in medulla of brain and
receptors in carotid bodies and aortic arch are
highly sensitive to the changes in pH of blood.
• Any fall in blood pH or increase in p CO2
stimulates ventilation.
• This reflex hyperventilation removes carbon
dioxide and hence by mass action reduces H+
ion concentration.

24. Role of hemoglobin
• Hemoglobin serves as a strong buffer in deoxygenated
state
• Its buffering capacity increases as the oxygen is lost into
the tissues.
• The peripheral tissues produce carbon dioxide as a result
of metabolism.
• This carbon dioxide is transported as bicarbonate ion
with minimum possible changes in pH

25. • 10 % CO2 is dissolved in plasma, 15% CO2 is
transported as carbamino haemoglobin(
bound to amino groups of aminoacids)
• 75% of CO2 is transported from tissues to
lungs as inorganic bicarbonate.

26. Chloride shift/Hamburger phenomenon

28. Reverse of chloride shift in lungs

30. Role of kidneys in regulation of pH
• Kidneys are the ultimate hydrogen ion balancers
• Kidneys provide a permanent mechanism to regulate
acid base balance of the body.
• The average p H of urine is 6.0, this shows the
excretion of hydrogen ions by kidneys.
• However the p H of urine can vary from 4.4 to 9.8 in
different conditions
• Carbonic anhydrase enzyme is present in high
concentration in renal tubular cells

32. Excretion of H+ ions
• Site: proximal tubular cells
• Purpose:1. to generate the bicarbonate ions
• 2. to increase the alkali reserve
• 3. to excrete hydrogen ion
• Result:1. new bicarbonate is generated
• 2. hydrogen ion is excreted
• This mechanism increases during acidosis due
to increased activity of carbonic anhydrase

33. 1. Excretion of H+ ions

34. 2. Reclamation of bicarbonate ions
• Site: proximal tubular cells
• Purpose: to reabsorb the filtered bicarbonate
• Result: no new bicarbonate is generated
• The bicarbonate is not lost in urine
• The process does not add to acidity of urine.

35. 2. Reabsorption of HCO3

36. 3.Excretion of titrable acids
• Definition of titrable acidity: the no. of
millilitres of N/10 NaOH required to titrate 1
litre of urine to pH 7.4
• It is a measure to net acid excretion by the
kidneys
• One of the major mechanisms operating
during acidosis.

37. • Site: distal convoluted tubules and collecting
ducts
• These cells have hydrogen ion ATPase in apical
cell membrane
• Purpose: to excrete acids by excreting sodium
dihydrogen phosphate
• The acid and base phosphate pair is called
urinary buffer
• Maximum limit of acidification is p H 4.5

39. 4. Excretion of ammonium ions
• Site: distal convoluted tubules
• Purpose: to trap the hydrogen ions in urine so
that large quantity of acids can be excreted
without changing the p H of urine.
• Glutaminase enzyme is present in tubular cells
• This mechanism also conserves sodium and
potassium
• Glutaminase activity is increased in acidosis

40. 4.Excretion of NH4 ions

41. Anion gap
• Definition: It is the difference between measured cations
and measured anions in plasma
• Calculation: Na+ K - ( Cl+ HCO3)
• There is no true gap between cations and anions . But in
laboratories only Cl and HCO3 are estimated which
constitute 85% of the anions ( unmeasured anions are
albumin, SO4, organic acids, phosphates etc
• Na and K make 95% of cations

44. Clinical significance of anion gap
• Normal AG is 12-16mmol/L
• Some acid base disorders have high anion gap:
( HAGMA)
• Ketoacidosis,
• uremia,
• lactic acidosis,
• salicylate poisoning,
• methanol intoxication,
• ethylene glycol poisoning

45. Normal anion gap metabolic acidosis
( NAGMA)
• Diarrhoea
• Renal tubular acidosis
• Ureteric implantation
• Acetazolamide therapy
Low anion gap:
• Hypoalbuminemia
• Multiple myeloma
• hypercalcemia

46. Metabolic acidosis
Definition: It is an acid base disorder where the p H of
plasma is lower than 7.35 due to primary deficit in
plasma bicarbonate levels.
Types/ classification:
Metabolic acidosis is classified depending on the anion
gap as:
• HAGMA( HIGH ANION GAP METABOLIC ACIDOSIS)
• NAGMA( NORMAL ANION GAP METABOLIC ACIDOSIS)

47. HAGMA
• Ketoacidosis:
• It can occur in uncontrolled type 1 diabetes
mellitus or prolonged starvation
• Acetoacetate and betahydroxybutyrate are the
anions accumulating.
• Lactic acidosis:
• normal lactic acid in plasma is less than 2
mmol/L.
• It is increased in tissue hypoxia, circulatory
failures and intake of drugs like biguanides

48. Types of lactic acidosis:
Type A: IMPAIRED LACTIC ACID PRODUCTION WITH
HYPOXIA:
Causes:
• anaerobic metabolism,
• shock,
• CO poisoning,
• cardiac failure

49. Type B: IMPAIRED LACTIC ACID METABOLISM
WITHOUT HYPOXIA
• Causes:
• liver dysfunction
• Oxidative phosphorylation disorders
• Thiamine deficiency

50. Other causes of HAGMA
• Renal failure: decreased renal acid excretion and
decreased NH4 ion excretion leads to accumulation
of organic anions , sulphuric and phosphoric anions
• Methanol poisoning, salicylate poisoning, ethylene
glycol intoxication, organic acidurias

51. Normal anion gap metabolic acidosis
• When there is loss of both anions and
cations, anion gap will remain normal
despite of acidosis
• Causes:
• hypochloremic acidosis: diarrhoea: loss
of intestinal secretions including
bicarbonate, sodium and potassium

52. • Hyperchloremic acidsosis:
• Renal tubular acidosis,
• Ureteric implantation
• Drugs like acetazolamide

53. Renal tubular acidosis

54. Clinical features
• Headache, nausea, unconsciousness, coma
• Rapid and deep breathing: Kussmaul breathing
• Edema : renal failure
• Muscle twitching
• Fall in BP

55. Laboratory investigations
• Arterial blood gas analysis reveals:
• p H: < 7.35 ( LESS THAN 7.2 is incompatible with life)
• P CO2: <40 mm Of Hg ( depending on the degree of
compensation)
• HCO3< 22 mmol/L
• K+ levels: high
• Anion gap: > 16 mmol/l in HAGMA , normal in other cases

56. • Urine: p H acidic, sugar ++ in DKA,
ketone bodies ++ in ketoacidosis
• Urinary anion gap -70mmol/l

57. Compensatory mechanisms
• Respiratory compensation : increased rate and depth
of respiration( kussmaul breathing)
• Minimum p CO2 is 15mm of Hg
• Renal compensation: increase in:
• Excretion of H+.
• Reabsorption of HCO3,
• Excretion of titrable acids,
• Excretion of NH4 ions

58. Management
• Correction of dehydration by IV fluids
• Monitor potassium levels
• Injection sodium bicarbonate.
• Injection of insulin: in DKA
• Dialysis in uremia
• Oxygen therapy: lactic acidosis

59. Metabolic alkalosis
• Definition: it is an acid base disorder in which
the p H of plasma rises above 7.45 due to
primary excess of bicarbonate
• Alkalosis occurs when:
• Excess of base is added
• Base excretion is defective
• Acid is lost

60. classification
• Chloride responsive : urinary chloride is less
than 10 mmol/l
• Alkalosis responds to administration of NaCl
• Chloride resistant: urinary chloride>20 mmol/l
• Cannot be treated with NaCl

61. Chloride responsive metabolic alkalosis:
• Prolonged vomiting, nasogastric suction, upper
GI obstruction
• Administration of loop diuretics: blocks
reabsorption of Na, K and Cl
• Loop diuretics administration leads to
secondary hyperaldosteronism which causes
Na retention and excretion of H+ and K+

62. Chloride resistant alkalosis
• Hypertension
• Hyperaldosteronism
• Cushing’s syndrome, adrenal tumor
• Iatrogenic: (excess base intake): milk alkali
syndrome, antacids, sodium citrate overload

63. Clinical features
• Depressed breathing
• Muscle twitching: increased neuromuscular activity
when p H is above 7.55
• Tetany: carpo-pedal spasm, even with normal
serum calcium levels
• Tachycardia
• Muscle weakness

64. Laboratory findings
• p H: >7.45
• P CO2 >45 mm of Hg( CANNOT BE ABOVE 55 mm of
Hg)
• HCO3 >26mmol/L
• serum K+ : low
• Calcium: decreased ionised calcium due to increased
charge on albumin. More calcium bound to albumin
• Urinary p H low( paradoxical aciduria)

65. Urinary chloride levels will depend on the type of
alkalosis:
• < 10mmol/l chloride responsive
• >20mmol/l chloride resistant

66. Compensatory mechanism
• Respiratory compensation: The rise in p H will depress the
chemoreceptors in respiratory centre
• The respiration will get depressed: decreased rate and depth
: to conserve CO2.
• Renal compensation will take place in 2-3 days:
There will be decreased:
• Excretion of H+
• Reabsorption of HCO3
• Excretion of titrable acids
• Excretion of NH4+

67. Management
It depends on etiology and volume status of the
patient
Etiology treatment
vomitting antiemetics
Prolonged gastric aspiration Proton pump inhibitors
Loop diuretics K sparing diuretics like
acetazolamide
Chloride responsive alkalosis IV NaCl ( 0.9%)
Chloride resistant alkalosis IV KCl
hyperaldosteronism spironolactone
Cushing’s syndrome Surgery of the tumor

68. Sometimes dialysis is needed to correct
the metabolic alkalosis

69. Respiratory Acidosis
• Definition: it is an acid base disorder leading
to the decrease in plasma p H < 7.35 due to
primary excess in p CO2
It is a result of hypoventilation leading to
retention of CO2

70. Causes
Acute:
Central: Overdose of anaesthetic agents
overdose of sedatives
Peripheral: Status asthamaticus
Acute exacerbation of COPD
Rib fracture
Foreign body choking
Bronchopneumonia

71. CAUSES
Chronic:
Central: Neuromuscular paralysis
motor neurone disease
myasthenia gravis
Obesity hypoventilation
Peripheral: COPD
Scoliosis and kyphosis
Interstitial lung disease

72. Clinical features
• Decreased respiratory rate
• Hypotension
• Vasodilation( due to carbon dioxide
retention)
• Tremor
• Tachycardia
• Drowsiness
• Muscle weakness

73. Laboratory investigations
• Arterial blood gas analysis :
• p H: <7.35
• P CO2: >45 mm of Hg it can be as high as
70 mm of Hg
• HCO3 is normal in uncompensated cases
• Serum K+ : High
• Oxygen saturation will be low

74. Compensatory mechanisms
• Excess carbonic acid is buffered by the
haemoglobin and protein buffer systems
• Kidney responds to compensate by:
• Increasing H+ excretion
• Increasing HCO3 reabsorption
• Increasing excretion of titrable acid
• Increasing NH4+ excretion

75. Management
• Goal is to increase the exhalation of CO2
• Treatment depends on the underlying cause
• Nebulisation (for status asthmaticus)
• Ventilation therapy can be given
• IV HCO3 can be given depending on base deficit
• Antidote of sedative agents or muscle relaxant
can be given
• Intubation and ventilator support in severe
cases

76. Respiratory alkalosis
• It is an acid base disorder where the p H of
plasma is > 7.45 due to primary deficit in p
CO2
• It is a result of hyperventilation that washes
away CO2
• Ratio of NaHCO3/H2CO3 is >20

79. Compensation
Buffers:
• Early compensation occurs by proteins and intracellular
buffers
Renal compensation:
• Starts within 6 hours: max in 2-3 days
• There is decrease in:
• Excretion of H+
• Reabsorption of HCO3
• Excretion of titrable acid
• Excretion of NH4+

80. Treatment
• Rebreathing in same paper bag
• Holding breath as long as possible
• Sedation to relieve anxiety
• Muscle relaxants
• IV arginine chloride and ammonium
chloride
• Treatment of underlying cause

81. Interpretation of acid base
disorders
• P H :7.35-7.45
• HCO3: 22-26 mmol/L
• Base excess:-2 -+2 mmol/l
• p O2: 90-110 mm of Hg
• P CO2: 35-45 mm of Hg
• Oxygen saturation: >97%

82. Thank you