Acid base balance and imbalance( Acid- base disorder)

1. Acid Base Balance

2.  INTRODUCTION
 ACIDS & BASES
 TYPES OF ACIDS & BASES
 pH
 HH equation
 BUFFERS
 TYPES OF BUFFER (MECHANISM)
Content

3.  Acid-base regulation
–Regulation of hydrogen ion
• Buffer system
• Respiratory regulation
• Renal regulation

4. Why ToRegulate pH?
 To maintain homeostasis
 Regulates enzymatic functions

5. Acids And
Bases
 Acids
– Release protons (H) ;Eg-H2CO3 , HCL
 Bases
– Accept protons (H) ; Eg-HCO3
– Releases OH in aqueous solution :NaOH

6.  Strong acids
– Release large amount of Hydrogen ions
 Weak acids
– Release small amount of Hydrogen ions
 Strong bases
– Accept large amount of Hydrogen ions
 Weak bases
– Accept small amount of Hydrogen ions
Types of acid and base

7. pH
• pH= -log[H+]
• defined as negative log of H + ion concentration
• If [H+] is high, the solution is acidic  pH
• If [H+] is low, the solution is basic or alkaline pH
• Acids are H+ donors.
• Bases are H+ acceptors, or give up OH- in solution.

8. Normal Blood gas Value
– [H+] = 40nEq/L
– pH= 7.40 (7.35-7.45)
 – PaCO2 = 40 mm Hg(35-45)
 – HCO3 =24 mEq/L (22-26)

9. Henderson –Hasselblach equation
 pH = pKa + log base
 Acid or pH = pKa + log Salt
 Acid

10. ACIDS PRODUCED IN THE BODY
 1.Carbonic acid (H2CO3): It is the chief acid produced in the body in the
course of oxidation in the cells. Oxidation of C-compounds resulting in
CO2 production.
 2.Sulphuric acid (H2SO4): A strong dissociable acid produced during
oxidation of S-containing amino acids, e.g. cysteine/cystine and
methionine
 3.Phosphoric acid: Products of metabolism of dietary phosphoproteins,
nucleoproteins, and hydrolysis of phosphoesters
 4.Organic acids: Abnormal production and accumulation
 of certain intermediary organic acids from
 oxidation of carbohydrates, fats and proteins, under
 certain circumstances, e.g. pyruvic acid, lactic acid,
 acetoacetic acid, β-OH-butyric acid, etc.

11. Buffer
Buffers are solutions which can resist
changes
in pH when acid or alkali is added.
Buffer + H H buffer

12. Composition of Buffer Buffers are of two types:
 a. Mixtures of weak acids with their salt with a strong
 base or
 b. Mixtures of weak bases with their salt with a
 strong acid. A few examples are given below:
 i. H2CO3/NaHCO3 (Bicarbonate buffer)
 (carbonic acid and sodium bicarbonate)
 ii. CH3COOH/CH3COO Na (Acetate buffer)
 (acetic acid and sodium acetate)
 iii. Na2HPO4/NaH2PO4 (Phosphate buffer)

13. Types of Chemical Buffers
– Carbonic acid-bicarbonate –
 Buffering changes caused by organic and fixed acids
– Protein buffer system-Amino acids
– Minor buffering system-
– Phosphate –Buffer pH in the ICF

14. Buffer Systems in Body Fluids
Figure 27.7

15. Carbonic Acid-Bicarbonate Buffering System
 Common extracellular buffer
• base constituent, bicarbonate (HCO3 –),is regulated by
the kidney (metabolic component).
• carbonic acid (H2CO3), is under respiratory regulation
(respiratory component).

16. Buffering action of Bicarbonate Buffering System

17. Bicarbonate
buffer-
 Has the following limitations:
– Only functions when respiratory system and
control centers are working normally
–It is limited by availability of bicarbonate
ions (bicarbonate reserve).

18. Phosphate Buffer System
• Common intracellular buffer
• The phosphate buffer system is found to be effective at a
wide pH range, because it has more than one ionizable
group and the pKa values are different for both.

19. Buffering action of phosphate
buffer

20.  Proteins are made up of amino acids
 Amino acids have a central carbon with four
groups off of it:
1.a carboxyl group (COOH)
2.an amino group (NH2)
3.a hydrogen atom
4.an R group
.
Protein buffer system

21. Structure of amino acids

22. Contd..
.
 At neutral pH the carboxyl ion is present as
COO instead of COOH.
 Acidic medium – becomes COOH
 Basic medium – becomes COO.

23. Contd…
 Amino group is attached to the amino acid
central carbon: C - NH2.
 Neutral pH, the amino group is actually-
NH + rather than just NH .3 2
 Acidic medium – becomes NH3+
 Basic medium- becomes NH2

24. Contd.
.

25. Hemoglobin as buffer
• physiological buffering action of Hb is due to the
 “imidazole” group of amino acid “histidine”
• Imidazole N2 group, which can give up H+ (proton) and
accept H+ depending on the pH of the medium.

27. Chloride shift

28. Respiratory regulation
When alveolar ventilation increases
CO2 conc. In ECF decreases
H+ conc. decreases
Or vice versa.......

29. Respiratory regulation
Contd…
 Pulmonary expiration of CO2 balances metabolic
formation of CO2
– 1.2 mol/L of dissolved CO2 is present in the ECF
corresponding to pCO2 of 40mm/hg
– Rate of pulmonary ventilation is
inversely proportional to CO2 & pCO2
– So either pulmonary ventilation rate of CO2
– or its formation by tissues can change pCO2
in ECF.

30. Contd…
 Increasing alveolar ventilation decreases ECF
hydrogen ion conc. And raises pH
– If alveolar ventilation increases the pCO2 decreases.
– If alveolar ventilation decreases the
pCO2 increases.
– Twice rise of AV--rises pH of ECF by about 0.23
– Decrease of AV to ¼ -- decreases pH by 0.45

31. Contd…
 Increased Hydrogen ion conc. Stimulates
alveolar ventilation
 Change in alveolar ventilation rate is much
greater in reduced levels of pH than in
increased levels of pH

32. Hydrogen ion conc.
By RS
H conc. Falls below normal
Respiration is depressed
Alveolar ventilation decreases
H increases back to normal

36. pH of urine is normally acidic(6). This indicates that
the kidneys have contributed to the acidification of
Urine
 Kidney is responsible for excreting fixed acids
H+ ions generated in the body in normal
circumstances are eliminated by acidified urine
pH range of urine is between 4.4 -9.5 depending on
the concentration n of H+ ions i the blood

37. Renal mechanism of acid-
base regulation
 Kidneys regulate the blood pH by
A. Excretion of H+ ions
B. Reabsorption of bicarbonate (recovery of
bicarbonate)
C. Excretion of titratable acid (net acid excretion)
D. Excretion of NH4+

39.  Excretion of H+; Generation of Bicarbonate
 i. This process occurs in the proximal convoluted
 tubules
 ii. The CO2 combines with water to form carbonic
 acid, with the help of carbonic anhydrase. The H2CO3 then
ionizes to H+ and bicarbonate.
 iii. The hydrogen ions are secreted into the tubular lumen; in
exchange for Na+ reabsorbed.
 These Na+ ions along with HCO3– will be reabsorbed into the
blood.
 iv. There is net excretion of hydrogen ions, and net generation of
bicarbonate. So this mechanism serves to increase the alkali
reserve.

41.  Reabsorption of Bicarbonate
 In PCT due to presence Na+/H+ exchanger, H+ is secreted to the
luminal fluid in exchange Na+ is reabsorbed into blood
 The hydrogen ions secreted into the luminal fluid is required for
the reabsorption of filtered bicarbonate.
 Bicarbonate filtered through glomerulus is mostly reabsorbed in
PCT by this mechanism
 The bicarbonate combines with H+ in tubular fluid to form
carbonic acid. It dissociates into water and CO2. The CO2 diffuses
into the cell, which again combines with water to form carbonic
acid.
 In the cell, it again ionizes to H+ that is secreted into lumen in
exchange for Na+. The HCO3– is reabsorbed into plasma along
with Na+.
 there is no net excretion of H+ or generation of new bicarbonate.

43.  Excretion of H+ as Titratable Acid
 In the distal convoluted tubules net acid excretion occurs. Hydrogen
ions are secreted by the distal tubules and collecting ducts by hydrogen
ion-ATPase located in the apical cell membrane.
 The hydrogen ions are generated in the tubular cell by a reaction
catalyzed by carbonic anhydrase. The bicarbonate generated
 within the cell passes into plasma.
 The term titratable acidity of urine refers to the number of milliliters
of N/10 NaOH required to titrate 1 liter of urine to pH 7.4. This is a
measure of net acid excretion by the kidney.
 The major titratable acid present in the urine is sodium acid
phosphate.

45.  Excretion of Ammonium Ions
 Predominantly occurs at the distal convoluted tubules. This
would help to excrete H+ and reabsorb HCO3–
 The Glutaminase present in the tubular cells can hydrolyze
glutamine to NH3 and glutamic acid. The NH3 (ammonia)
diffuses into the luminal fluid and combines with H+ to form
NH4+(ammonium ion).
 Binding of H+ to NH3 will resist the decrease of pH of urine

51. Disorders of acid-base
regulation
 MAY LEAD TO---------
 ALKALOSIS(>7.45)
OR
ACIDOSIS(<7.35)

52. • Respiratory acidosis (excess of
H2CO3)
• Metabolic Acidosis( decrease in
HCO3- or increased acid production)Acidosis
• Respiratory Alkalosis( decrease in
H2CO3)
• Metabolic Alkalosis( Increase in
bicarbonate)
Alkalosis
Respiratory acid-base disorders are initiated by an increase or
decrease in partial pressure of carbondioxide(pCO2) whereas
metabolic disorders are initiated by an increase or decrease in
bicarbonate ion(HCO3-)

53. Disorders of acid-base regulation
cont…

54. Compensatory Mechanism In Acid –base disorder
•If underlying problem is metabolic, hyperventilation or hypoventilation can
help: Respiratory Compensation
•If Problem is Respiratory, Renal mechanism can retain or excrete bicarbonate
and bring about metabolic compensation

55. Respiratory acidosis
primary excess of carbonic acid is the cardinal feature
It is due to CO2 retention as a result of hypoventilation
HCO3-/H2CO3 <20
Causes: (DEPRESS)
D- Drugs(opioids, sedatives)Diseases of neuromuscular
system
E-Edema( pulmonary)
P- Pneumonia
R-Respiratory centre of brain damaged(brain injury, stroke)
E-Emboli( blocking pulmonary artery)
S-Spasms of bronchial tubes( asthma)
S-Sac(Alveolar) elasticity damaged( Emphysema, COPD)

57. Compensation of respiratory acidosis
 Carbonic acid is buffered by blood buffers
 Kidney excretes more H+ and reabsorbs HCO3-
 Hyperventilation

58. Respiratory Alkalosis
 A primary deficit of carbonic acid is described as
the respiratory alkalosis.
 Hyperventilation will result in washing out of CO2
 HCO3-/H2CO3 >20:1
Causes:
High altitude
Hysteria
Febrile conditions

60. Compensation of Respiratory
alkalosis
 Release of H+ from blood buffer systems
 decrease absorption of bicarbonate from kidney
 Hypoventilation

61. Anion Gap
 The sum of cations and anions in ECF is always equal, so
as to maintain the electrical neutrality.
 Sodium and potassium together account for 95% of the
cations whereas chloride and bicarbonate account for
only 86% of the anions.
 Only these electrolytes are commonly measured in
laboratory.
 Hence there is always a difference between the measured
cations and the anions.
 The unmeasured anions constitute the anion gap.
 Unmeasured anion are protein anions,sulphate,
phosphate and organic acids.

62. Protein 16
AG

64. If an acid is added to blood
Anion H+ Na+ HCO3
-+
Na
Cl H CO3 UnHCO3

65. Na
Cl HCO3 Un
Cl- Other Anion
Normal Anion gap
Metabolic Acidosis
(Hyperchloremic)
High Anion gap
Metabolic Acidosis

67. High anion Vs Normal anion gap acidosis
 High anion gap metabolic acidosis: It is due to
over production of acids that contributes anion and
uses bicarbonate. For example production of lactic
acid contributes lactate ion and H+. H+ binds
with bicarbonate. As a result there is increase in
unmeasured anion( lactate) and bicarbonate
decreases and finally results in high anion gap
metabolic acidosis.
 Normal anion gap metabolic acidosis: a loss of
both anions and cations,the anion gap is normal,
but acidosis may prevail.
Eg; Diarrhea ( loss of HCO3-, Na+ and K+)
Hyperchloremic acidosis may occur in renal
tubular acidosis(Renal tubular acidosis)

69. UNa+ + UK+ + Unmeasured cations = UCl- + Unmeasured anions
Or, Unmeasured anions – Unmeasured cations = (UNa+ + UK+) - UCl-
Urine Anion Gap (UAG) = (UNa+ + UK+) -UCl-
- NH + is the primary unmeasured cation which is not balanced by anions.
4
- UAG as indirect assay for renal NH4+ excretion
Na K
+
NH4
Cl
The normal value is –20 to –50 mmol/L.

70. Negative Positive
Increased renal
NH4+ excretion
(Response to acidemia)
GI loss of HCO3-
RTA II
Failure of Kidneys
4to secrete NH +
RTA I and RTA IV

71. Causes of High anion gap metabolic acidosis(HAGMA)
MUDPLIES Retained Acids
 M- Methanol intoxication Formic acid
 U-Uremia ( Sulfuric, Phosphoric,organic)
 D- Diabetic Ketoacidosis (Acetoacetate/behydroxybytyrate)
 P-Paraldehyde and propylene glycol (Organic acids)
 I- Isoniazid , Iron toxicity ( mainly lactic acid)
 L- Lactic acid (lactic acid)
 E- Ethylene glycol toxicity (glycolate and oxalate)
 S- Salicylate ( Salicylic acid, organic)

72. Causes of Normal Anion gap metabolic acidosis
 Diarrhea ( loss of HCO3- and Na+ and K+)
 Renal tubular acidosis
Proximal RTA( Type II)
Distal RTA( Type I)
Type IV( decrease aldosterone)
In all of the causes above there is loss of HCO3- with
compensatory reabsorption of Chloride.
Therefore not changing anion gap.

75. Metabolic Alkalosis
 Primary excess of bicarbonate is the characteristic
feature. Alkalosis occurs when
a) excess base is added, b) base excretion is defective or
c) acid is lost.
Increased HCO3-/H2CO3 > 20:1

76. Metabolic Alkalosis
Chloride Responsive
Urine Cl- < 20 mEq/L
Causes
•
•
•
•
• Volume Contraction:
– Nasogastric suctioning, Gastric fistula
– Vomiting , pyloric stenosis
– Lowchloride intake
• Alkali therapy (NaHCO3, Antacid abuse)
• Chloride depletion (Diarrhoea & Diuretics
36

77. Metabolic Alkalosis
Chloride Unresponsive (resistant)
• Mineralcorticoid excess e.g Hyperaldosteronism
• Exogenous steroids, Cushing’s disease
•
•
Alkali Ingestion
Bartter’s Syndrome
Urine Cl- > 20 mEq/L
37

80. Arterial Blood Gas(ABG) Analysis
 The assessment of acid-base status is usually done by
the arterial blood gas (ABG) analyzer
 Radial artery is commonly chosen
Parameters of ABG analysis
 Normal ABG Values
 pH : 7.35-7.45
 PaCO2 : 35-45 mmHg.
 HCO3 : 22-26 mEq/L
 PaO2 : 70-100 mmHg.
 SaO2 : 93-98%

81. Other Parameters with ABG
 Measurement of Electrolytes(Na, K, Cl)and
calculation of Anion gap along with ABG analysis
helps in knowing the Acid- base status and the causes.

82. ABG analysis Interpretation

83. Is there any (if any) compensation
occurring?
 No compensation: pH remains abnormal, and the ‘other’ value
(where the problem isn’t occurring, i.e. PCO2 or HCO3- ) will remain
normal or has made no attempt to help normalise the pH. For
example: in uncompensated metabolic acidosis: pH =7.23, HCO3-
6 15mmol/L, and the PCO2 will be normal at 40mmHg.
 Partial compensation :pH is still abnormal, and the ‘other’ value is
abnormal in an attempt to help normalise the pH. For example: in
partially compensated respiratory alkalosis: pH =7.62, PCO2 =27
and the HCO3- will be abnormal at 17mmol/L
 Full compensation: The pH is normal, as the ‘other’ value is
abnormal and has been successful in normalising the pH. For
example: Fully compensated metabolic acidosis pH= 7.38, HCO3-
=15mmol/L and the CO2 =30mmHg

85. ABG findings in Acid –base disturbances

86. Example
• A patient is in intensive care because he suffered
a severe myocardial infarction 3 days ago. The
lab reports the following values from an arterial
blood sample:
– pH 7.3
– HCO3- = 20 mEq / L ( 22 - 26)
– pCO2 = 32 mm Hg (35 - 45)
Diagnosis
• Metabolic acidosis
• With partial compensation
52

87. CASE 1
• A 44 year old moderately dehydrated man
was admitted with a two day history of acute
severe diarrhea. Electrolyte results: Na+ 134,
K+ 2.9, Cl- 108, HCO3- 16,
• Urea 31, Cr 1.5.
•
ABG: pH =7.31 pCO2- 33 mmHg
HCO3 =16 pO2-93 mmHg
53

88. CASE 2
•
•
•
A 22 year old female with type I DM, presents to the
emergency department with a 1 day history of nausea,
vomiting, polyuria, polydypsia and vague abdominal pain.
Labs: Na 132 , K 6.0, Cl 93, HCO3- 11 glucose 720, Urea 38,
Cr 2.6.
UA: pH 5, SG 1.010, ketones negative, glucose positive .
Plasma ketones trace.
ABG: pH- 7.27 HCO3- 10 PCO2 -23
What is the acid base disorder?
54

89. CASE 3
• A 70 year old man
with history of CHF
presents with
increased shortness
of breath and leg
swelling.
ABG: pH 7.24, PCO2
60 mmHg, PO2 52
HCO3- 27
• What is the acid
base disorder? 55