This document provides an overview of acid-base balance and disorders. It begins with an introduction to normal acid-base balance and the buffer systems that maintain it. It then discusses the four main types of acid-base disorders: metabolic acidosis, metabolic alkalosis, respiratory acidosis, and respiratory alkalosis. Specific causes, clinical presentations, and treatments are described for different forms of metabolic and respiratory acid-base disturbances. Renal tubular acidosis is examined in depth, with descriptions of types 1, 2, and 4 RTA. Calculation methods for diagnosing and evaluating acid-base disorders are also covered.

1. Acid-Base Balance & Disorders
.
Part I .
Normal Acid Base Balance
&
Metabolic Acid Base Disorders
Presented By
dr. Mohammed Abdel Gawad
Nephrologist

3. To download the lecture contact me
drgawad@gmail.com
More lectures on www.NephroTube.com

4. Acid Base Balance & Disorders
• Normal Acid Base Balance
• Metabolic Acidosis
• Metabolic Alkalosis
• Respiratory Acidosis
• Respiratory Alkalosis
• Mixed Acid Base Disorders
• ABG Interpretation
4
Part I
Part II

5. Acid Base Balance & Disorders
• Normal Acid Base Balance
• Metabolic Acidosis
• Metabolic Alkalosis
• Respiratory Acidosis
• Respiratory Alkalosis
• Mixed Acid Base Disorders
• ABG Interpretation
5
Part I
Part II

6. Acid-base physiology is not hard

8. pH
• Power of hydrogen
• Potential of hydrogen
pH Scale

9. Lactic acid Sulphuric acid
Carbonic acid
Phosphoric acid
Threats to pH
• 1. Volatile acids: Carbon dioxide:
• 2. Fixed-non volatile acids:
▫ a- Sulphuric acid:
●
an end product of the oxidation of sulphur containing aminoacids, methionine
and cysteine.
▫ b- phosphoric acid:
●
formed in the metabolism of phospholipids, nucleic acids, phosphorproteins and
phosphoglycerides.
• 3. Organic acids:
▫ Lactic acid, acetoacetic acid and B-OH-butyric acid
●
formed during the metabolism of carbohydrates and fats.

10. Only free hydrogen
ion is physiologically active
When plasma hydrogen is measured in hospital labs, only free hydrogen
concentration is measured and reported as pH.

11. Defense against changes in H+ concentration
• I. Acid-base buffer systems in body fluids,
within seconds.
• II. The respiratory system,
within minutes.
• III. The kidneys,
within hours.
BufferWeak Acid + Strong Base
or
Weak Base + Strong Acid
• A. The bicarbonate buffer system
• B- The phosphate buffer system
• C- The protein buffer system

12. I-acid-base buffers
A. The bicarbonate buffer system
• consists of a mixture of:
▫ carbonic acid (H2CO3) and sodium bicarbonate (NaHCO3) in the same body
fluid.
• When a strong acid, as hydrochloric acid, is added:
• When a strong base, as sodium hydroxide, is added:
• It is the most important buffer system in the body because:
▫ 1- present in all the body fluids, both ECF & ICF.
▫ 2- concentration of its components (CO2 & HCO3)can be independently
regulated
HCl + NaHCO3 H2CO3 + NaCl
NaOH + H2CO3 NaHCO3 + H2O

13. Defense against changes in H+ concentration
• I. Acid-base buffer systems in body fluids,
within seconds.
• A. The bicarbonate buffer system
• B- The phosphate buffer system
• C- The protein buffer system

14. I- acid-base buffers
B- The phosphate buffer system:
• composed of:
• more effective in ICF than in ECF:
▫ The total concentration of phosphate is much greater in ICF than ECF.
• also effective in buffering the tubular fluid in the kidneys because:
▫ Phosphate becomes greatly concentrated in the tubular fluid due to the
reabsorption of water in excess of phosphate.

15. Defense against changes in H+ concentration
• I. Acid-base buffer systems in body fluids,
within seconds.
• A. The bicarbonate buffer system
• B- The phosphate buffer system
• C- The protein buffer system

16. I- acid-base buffers
C- The protein buffer system
• 1) Proteins of the cells and the plasma:

17. 17
CO2
Red Blood Cell
Systemic Circulation
H2O
H+ HCO3-
carbonic
anhydrase
Plasma
CO2 CO2 CO2 CO2 CO2CO2
+ +
Tissues
H+
Cl-
Hb
H+ is buffered by
Hemoglobin
I-acid-base buffers
C- Protein buffer
system
2) Haemoglobin
Tissue side

18. 18
Red Blood Cell Pulmonary Circulation
CO2 H2O
H+
+ + HCO3-
Cl-
Alveolus
Plasma
CO2
CO2 H2O
Hb
Lung side

19. Defense against changes in H+ concentration
• I. Acid-base buffer systems in body fluids,
within seconds.
• II. The respiratory system,
within minutes.
• III. The kidneys,
within hours.

20. II- Respiratory regulation of acid-base balance

21. Defense against changes in H+ concentration
• I. Acid-base buffer systems in body fluids,
within seconds.
• II. The respiratory system,
within minutes.
• III. The kidneys,
within hours.

22. 1- Reabsorption (Reclamation)of the
filtered bicarbonate - PCT

23. 2. Generation of new bicarbonate
A- ammonia (PCT & DCT)

24. 2. Generation of new bicarbonate
B- phosphate (DCT)

25. pH Scale

26. Co2 is an acid
While
HCO3 is a base
Normal Values
Parameter Normal value
pH 7.35 – 7.45
PCO2 35 – 45 mmHg
HCO3 22- 26 mEq/L

27. Classification of Acid-basic Disorders
pH PCO2 HCO3
Metabolic
Acidosis
↓ ↓
(compensation)
↓
(1ry disorder)
Metabolic
Alkalosis
↑ ↑
(compensation)
↑
(1ry disorder)
Respiratory
Acidosis
↓ ↑
(1ry disorder)
↑
(compensation)
Respiratory
Alkalosis
↑ ↓
(1ry disorder)
↓
(compensation)

29. Henderson–Hasselbalch equation
pH = log 1 / H+

30. Acid Base Balance & Disorders
• Normal Acid Base Balance
• Metabolic Acidosis
• Metabolic Alkalosis
• Respiratory Acidosis
• Respiratory Alkalosis
• Mixed Acid Base Disorders
• ABG Interpretation
30
Part I
Part II

31. I- Approved metabolic acidosis:
• pH < 7.35
• HCO3 < 22 mEq/L
• PCO2 < 35 mmHg (compensation)
• for each 1 HCO3 1.2 CO2↓ → ↓
▫ or
• Δ ↓ Pco2 = 1.2 x ΔHCO3
• In absence of full compensation, this is
called:
▫ A- partial compensation
▫ or better called:
▫ B- mixed metabolic & respiratory acidosis:
as the lung not washing enough CO2 as needed, which mean that it is actually accumulating CO2
II- Expected compensation:

32. NormocholeremicHypercholeremic
III- Calculate
Anion Gap

33. III- Calculate Anion Gap
• Equations:
▫ AG = (Na + K) – (Cl + HCO3) = 12 ± 4 mmol/l
▫ or
▫ AG = (Na) – (Cl + HCO3) = 12 ± 2 mmol/l
• Corrected Anion Gap:
▫ anion gap is decreased by 4 mmol/l for each 1 g/dl decrease in the
serum albumin concentration below normal.
• The result:
▫ Wide (high) anion gap metabolic acidosis
▫ or
▫ Non (normal) anion gap metabolic acidosis

34. High AG acidosis
•
•
•
•
•
•
•
•
K
U
S
S
M
A
L
E
Ketoacidosis (starvation, DM, alcohol)
Uremia
Sepsis
Salicylate & other drugs e.g.paraldhyde
Methanol
Alcohol (Ethanol)
Lactic acidosis
Ethylene glycol
Wide Anion Gap Causes
Normocholeremic

35. 4- uretrosigmoid-
ostomy
Non Anion Gap Causes
Hypercholeremic

36. To remember
• I- Approved Metabolic Acidosis
• II- Calculate Compensation
• III- Calculate Anion Gap
• IV-
– a- if high anion gap calculate delta gap→
– b- if normal anion gap calculate urinary AG→

37. ●
IV- a- if high anion gap calculate delta gap→
∆ Gap = ∆AG / ∆HCO3
▫ = 1
= simple high AG metabolic acidosis
▫ > 1
= high AG metabolic acidosis mixed with metabolic
alkalosis
▫ < 1
= high AG metabolic acidosis mixed with non AG
metabolic acidosis
Ketoacidosis
Uremia
Sepsis
Salicylate & other drugs
Methanol
Alcohol (Ethanol)
Lactic acidosis
Ethylene glycol
AG
HCO3
Cl
12
24
AG
HCO3
AG
HCO3
AG
HCO3
AG
HCO3
AG
HCO3
AG
HCO3

38. ●
IV- b- if normal anion gap calculate urinary→
AG
4- uretrosigmoid-
ostomy

39. ●
IV- b- if normal anion gap calculate urinary→
AG
4- uretrosigmoid-
ostomy
urine AG = u[Na + K] – u[Cl]
If –ve:
so the loss is non renal
If zero or +ve:
so the loss is renal
N.B.
Normally it is +ve ranging from
+30 to +50 mmol/L

40. To remember
• I- Approved Metabolic Acidosis
• II- Calculate Compensation
• III- Calculate Anion Gap
• IV-
– a- if high anion gap calculate delta gap→
– b- if normal anion gap calculate urinary AG→

41. 41
Metabolic Acidosis Treatment
• Treatment of metabolic acidosis usually involves
either sodium bicarbonate or citrate:
• A- Sodium bicarbonate:
• orally as tablets or powder
• or given intravenously as a
●
1- hypertonic sodium bicarbonate bolus
●
or
●
2- an isotonic sodium bicarbonate infusion (adding three
●
ampules of sodium bicarbonate (50 mmol/amp) to a
●
liter of 5% dextrose in water (D5W) solution.
• B- Sodium Citrate:
• orally as a liquid, as sodium citrate, potassium citrate, or citric acid
and as a combination of these.
• Oral citrate therapy should not be combined with medications
that include aluminum.

42. Bicarbonate Deficit – Equation 1

43. Bicarbonate Deficit – Equation 2

45. Bicarbonate Administration
• Koda-Kimble et al:
• Replace 50% over 3 to 4 hours
• the reminder over 24 hours.
• Once the pH is 7.2 - 7.25, the serum [HCO3-]
should not be increased by more than 4 to 8
Eq/L over 6 to 12 hours to avoid the risks of
over-alkalinization (paradoxical CNS acidosis;
decreased affinity of hemoglobin for oxygen
leading to tissue hypoxia and lactic acid
production; sodium overload; and hypokalemia).

53. Renal Tubular Acidosis

54. Proximal Tubule
Reabsorption:
• HCO3-
(90%)
• calcium
• glucose
• Amino acids
• NaCl, water
• Secretion:
• H+
Distal Tubule
• Na+ reabsorbed
• molar
competition
between H+ and
K+ excretion
• under effect of
aldosterone
Renal Tubular Acidosis cont.
Normal Tubules Transport

55. Functions of DCT & Collecting Duct
Aldosteron

56. Renal Tubular Acidosis - Types
Type 2 RTA Type 1 RTA
Type 4 RTA

57. Renal Tubular Acidosis - Types
Type 2 RTA Type 1 RTA
Type 4 RTA

58. • Distal defect 
▫ A- impaired H+ secretion (secretory defect)
▫ Or
▫ B- defect in the basolateral anion exchanger
AE1 → abnormally permeable distal tubule →
resulting in increased backleak of normally
secreted H+ (gradient defect)
• Net result
▫ A- H+ builds up in blood (acidosis)
▫ B- Urine pH > 5.5
▫ C- K+ secreted instead of H+ (hypokalemia)
▫ D- The subsequent metabolic acidosis →
stimulates reabsorption of bone matrix to
release the calcium alkali salts present in
bone.
Type 1 RTA (classical distal RTA –
Hypokalemic RTA)
Site of
defect
❶
❷

59. • Growth retardation
• Bone disease
• Kidney stones
• Intermittent muscle weakness (hypokalemia)
• Progressive renal failure as a result of:
▫ a- underlying disease
▫ a- hypokalemia induced interstitial fibrosis.
Type 1 RTA - Presentation

60. Click to edit Master text styles
Second level
● Third level
● Fourth level
● Fifth level

62. Type 1 RTA - When to suspect ?
• Type 1 RTA should be suspected in a patient
with:
▫ a non anion gap metabolic acidosis
▫ &
▫ hypokalemia
▫ &
▫ urine pH above 5.5 in the setting of systemic acidosis
▫ &
▫ UAG value ≥ zero.

63. Type 1 RTA
Causes

64. Type 1 RTA - Treatment
• Treat the cause.
• Alkali replacement:
▫ 1-3mmol/kg/day bicarbonate
• Potassium replacement if hypokalemia

65. Renal Tubular Acidosis - Types
Type 2 RTA Type 1 RTA
Type 4 RTA

66. Renal Tubular Acidosis - Types
Type 2 RTA Type 1 RTA
Type 4 RTA

67. • Aldosterone deficiency
or distal tubule
resistance to
aldosterone 
▫ impaired function of
Na+/K+-H+ exhange
mechanism 
▫ Decreased H+ and K+
secretion 
▫ plasma buildup of H+
and K+
Defect in
aldosteron
action
Type 4 RTA (Hyperkalemic Distal RTA)

68. Distal Renal Tubular Acidosis
Type 1 RTA
LOW serum K+
Type 4 RTA
HIGH serum K+

69. Type 4 RTA
• Urine pH:
▫ Variable

70. Type 4 RTA
Causes

71. Type 4 RTA - Treatment
• 1- treat the cause
• 2- if due to hypoladosteronism:
▫ Give fludrocortisone 0.1 mg/d
• 3- if secondary to drugs (ACEI, Spironolactone):
▫ Advice low K diet
▫ Mineralocorticoides of no significance to avoid Na retension.
• 4- Loop & thiazide diuretics
• 5- NaHCO3 for acidosis & hyperkalemia (but watch
overload & worsening HTN)

72. Renal Tubular Acidosis - Types
Type 2 RTA Type 1 RTA
Type 4 RTA

73. Renal Tubular Acidosis - Types
Type 2 RTA Type 1 RTA
Type 4 RTA

74. Type 2 RTA (Proximal RTA)
•Urine pH:
▫ Decreased reabsorption of HCO3 HCO3- wasting
▫  Urine pH high initially then
▫  the filtered bicarbonate load decreases to the point at which the
proximal tubule is able to reabsorb sufficient filtered bicarbonate.
▫ When this process occurs, no further bicarbonate is lost in the
urine, net acid excretion normalizes, and a new steady-state
serum bicarbonate concentration develops, albeit at a lower
than normal level  Urine pH< 5.5

75. • Hypokalemia:
▫ Renal NaHCO3 losses → intravascular
volume depletion → activates RAS
system → increased distal nephron Na+
reabsorption & increased K+ secretion.
▫ In the steady state, when virtually all the
filtered HCO3− is reabsorbed in the
proximal and distal nephron, renal
potassium wasting is less and the degree
of hypokalemia tends to be mild.
Type 2 RTA (Proximal RTA)

76. Type 2 RTA (Proximal RTA) - Bone
• Osteomalacia can develop as a result of:
▫ A- chronic hypophosphatemia if Fanconi
syndrome is present.
▫ B- deficiency in the active form of vitamin D.

77. Type 2 RTA (Proximal RTA) – When to suspect ?
• Proximal RTA should be suspected in a patient with:
▫ a normal anion gap acidosis
▫ &
▫ hypokalemia
▫ &
▫ intact ability to acidify the urine to below 5.5 while in a steady
▫ &
▫ UAG ≥ zero.
▫ ±
▫ other proximal tubular dysfunction, such as euglycemic glycosuria,
hypophosphatemia, hypouricemia, and mild proteinuria.

78. Type 2 RTA
Causes

79. Type 2 RTA - Treatment
• A problem we face:
▫ Administration of alkali → increases the serum bicarbonate concentration,
→ increases urinary bicarbonate losses → increases distal sodium load →
increased circulating plasma aldosterone, → increased renal potassium
wasting.
▫ As a result, substantial amounts of alkali, often in the form of a potassium
bicarbonate required to prevent worsening hypokalemia.
• Alkali therapy:
▫ KHCO3 1.5 – 3 g/d in 3 divided doses.
• Vit D in infants

80. Type 3 RTA?
• Very rare
• Used to designate mixed dRTA and pRTA of
uncertain etiology
• Now describes genetic defect in Type 2 carbonic
anhydrase (CA2), found in both proximal, distal
tubular cells and bone

82. Acid Base Balance & Disorders
• Normal Acid Base Balance
• Metabolic Acidosis
• Metabolic Alkalosis
• Respiratory Acidosis
• Respiratory Alkalosis
• Mixed Acid Base Disorders
• ABG Interpretation
82
Part I
Part II

83. I- Approved metabolic alkalosis:
• pH > 7.45
• HCO3 > 26 mEq/L
• PCO2 > 45 mmHg (compensation)
• for each 1 HCO3 0.7 CO2↑ → ↑
▫ or
• Δ ↑ Pco2 = 0.7 x ΔHCO3
• In absence of full compensation, this is
called:
▫ A- partial compensation
▫ or better called:
▫ B- mixed metabolic & respiratory alkalosis:
as the lung can not retain enough CO2 as needed, which mean that it is actually washing CO2 even if
the PCO2 is higher than normal.
II- Expected compensation:

84. III- Causes
• A- Chloride Depletion (urine Cl < 10 mEq/L)
• B- Corticosteroid & Apparent Corticosteroid
Induced (chloride resistant) (urine Cl > 10 mEq/L)
• C- Alkali Administration or Ingestion

85. A- Chloride Depletion
(urine Cl < 10 mEq/L)

86. B- Corticosteroid & Apparent Corticosteroid Induced
(chloride resistant)
(urine Cl > 10 mEq/L)

87. C- Alkali Administration
or
Ingestion

89. 89
Metabolic Alkalosis Treatment
1- Treat the cause
2-

90. Thank You