This document discusses acid-base balance and disorders. It begins by defining acids and bases, and describing the normal physiology of acid-base balance. It then discusses the four main types of acid-base disorders: metabolic acidosis, metabolic alkalosis, respiratory acidosis, and respiratory alkalosis. For each disorder it describes the primary disturbance (pH or HCO3-) and the secondary compensatory response. The document goes on to provide details on the causes, mechanisms, and clinical assessments of different metabolic and respiratory acid-base disorders.

1. ACID BASE BALANCE
Dr Amith Sreedharan

2. DISCUSSION HEADINGS
• BASICS
• NORMAL PHYSIOLOGY
• ABNORMALITIES
• METABOLIC ACID BASE DISORDERS
• RESPIRATORY ACID BASE DISORDERS
• ALTERNATIVE CONCEPTS

3. • Acid
Any compound which forms H⁺ ions in
solution (proton donors)
eg: Carbonic acid releases H⁺ ions
• Base
Any compound which combines with
H⁺ ions in solution (proton acceptors)
eg:Bicarbonate(HCO3⁻) accepts H+ ions

4. Acid–Base Balance
Normal pH : 7.35-7.45
Acidosis
Physiological state resulting from abnormally low plasma pH
Alkalosis
Physiological state resulting from abnormally high plasma pH
Acidemia: plasma pH < 7.35
 Alkalemia: plasma pH > 7.45

5. Henderson-Hasselbach equation (clinically
relevant form)
• pH = pKa + log([HCO3-]/.03xpCO2)
• pH = 6.1 + log([HCO3-]/.03xpCO2)
• Shows that pH is a function of the RATIO
between bicarbonate and pCO2
• PCO₂ - ventilatory parameter (40 +/- 4)
• HCO₃⁻ - metabolic parameter (22-26 mmol/L)

6. ACIDS
• VOLATILE ACIDS:
 Produced by oxidative metabolism of CHO,Fat,Protein
 Average 15000-20000 mmol of CO₂ per day
 Excreted through LUNGS as CO₂ gas
• FIXED ACIDS (1 mEq/kg/day)
 Acids that do not leave solution ,once produced they
remain in body fluids Until eliminated by KIDNEYS
Eg: Sulfuric acid ,phosphoric acid , Organic acids
Are most important fixed acids in the body
Are generated during catabolism of:
amino acids(oxidation of sulfhydryl gps of cystine,methionine)
Phospholipids(hydrolysis)
nucleic acids

7. Response to ACID BASE challenge
1.Buffering
2. Compensation

8. Buffers
First line of defence (> 50 – 100 mEq/day)
Two most common chemical buffer groups
– Bicarbonate
– Non bicarbonate (Hb,protein,phosphate)
Blood buffer systems act instantaneously
Regulate pH by binding or releasing H⁺

9. Carbonic Acid–Bicarbonate Buffer System
Carbon Dioxide
 Most body cells constantly generate carbon dioxide
 Most carbon dioxide is converted to carbonic acid, which dissociates
into H+ and a bicarbonate ion
Prevents changes in pH caused by organic acids and fixed
acids in ECF
 Cannot protect ECF from changes in pH that result
from elevated or depressed levels of CO2
 Functions only when respiratory system and
respiratory control centers are working normally
 Ability to buffer acids is limited by availability of
bicarbonate ions

10. Acid–Base Balance
The Carbonic Acid–Bicarbonate Buffer System

11. The Hemoglobin Buffer System
CO2 diffuses across RBC membrane
No transport mechanism required
As carbonic acid dissociates
Bicarbonate ions diffuse into plasma
In exchange for chloride ions (chloride shift)
• Hydrogen ions are buffered by hemoglobin molecules
Is the only intracellular buffer system with an
immediate effect on ECF pH
Helps prevent major changes in pH when plasma PCO
2
is rising or falling

12. Phosphate Buffer System
Consists of anion H2PO4- (a weak acid)(pKa-6.8)
Works like the carbonic acid–bicarbonate buffer
system
Is important in buffering pH of ICF
Limitations of Buffer Systems
 Provide only temporary solution to acid–
base imbalance
 Do not eliminate H+ ions
 Supply of buffer molecules is limited

13. Respiratory Acid-Base Control
Mechanisms
• When chemical buffers alone cannot prevent
changes in blood pH, the respiratory system
is the second line of defence against changes.
Eliminate or Retain CO₂
Change in pH are RAPID
Occuring within minutes
PCO₂ ∞ VCO₂/VA

14. Renal Acid-Base Control Mechanisms
• The kidneys are the third line of defence
against wide changes in body fluid pH.
– movement of bicarbonate
– Retention/Excretion of acids
– Generating additional buffers
Long term regulator of ACID – BASE balance
May take hours to days for correction

15. Renal regulation of acid base balance
• Role of kidneys is preservation of body’s
bicarbonate stores.
• Accomplished by:
– Reabsorption of 99.9% of filtered bicarbonate
– Regeneration of titrated bicarbonate by excretion
of:
• Titratable acidity (mainly phosphate)
• Ammonium salts

16. Renal reabsorption of bicarbonate
• Proximal tubule:
70-90%
• Loop of Henle:
10-20%
• Distal tubule and
collecting ducts:
4-7%

17. Factors affecting renal bicarbonate
reabsorption
• Filtered load of
bicarbonate
• Prolonged changes in
pCO2
• Extracellular fluid
volume
• Plasma chloride
concentration
• Plasma potassium
concentration
• Hormones (e.g.,
mineralocorticoids,
glucocorticoids)

18. • If secreted H+ ions combine with filtered
bicarbonate, bicarbonate is reabsorbed
• If secreted H+ ions combine with
phosphate or ammonia, net acid excretion
and generation of new bicarbonate occur

19. NET ACID EXCRETION
• Hydrogen Ions
Are secreted into tubular fluid along
• Proximal convoluted tubule (PCT)
• Distal convoluted tubule (DCT)
• Collecting system

20. Titratable acidity
• Occurs when secreted
H+ encounter & titrate
phosphate in tubular
fluid
• Refers to amount of
strong base needed to
titrate urine back to pH
7.4
• 40% (15-30 mEq) of
daily fixed acid load
• Relatively constant (not
highly adaptable)

21. Ammonium excretion
• Occurs when
secreted H+ combine
with NH3 and are
trapped as NH4+ salts
in tubular fluid
• 60% (25-50 mEq) of
daily fixed acid load
• Very adaptable (via
glutaminase
induction)

22. Ammonium excretion
• Large amounts
of H+ can be
excreted
without
extremely low
urine pH
because pKa of
NH3/NH4+
system is very
high (9.2)

23. Acid–Base Balance Disturbances
Interactions among the Carbonic Acid–Bicarbonate Buffer System and
Compensatory Mechanisms in the Regulation of Plasma pH.

24. Acid–Base Balance Disturbances
decreased
Interactions among the Carbonic Acid–Bicarbonate Buffer System and
Compensatory Mechanisms in the Regulation of Plasma pH.

25. Four Basic Types of Imbalance
• Metabolic Acidosis
• Metabolic Alkalosis
• Respiratory Acidosis
• Respiratory Alkalosis

26. Acid Base Disorders
Disorder pH [H+] Primary Secondary
disturbance response
Metabolic    [HCO3-]  pCO2
acidosis
Metabolic    [HCO3-]  pCO2
alkalosis
Respiratory    pCO2  [HCO3-]
acidosis
Respiratory    pCO2  [HCO3-]
alkalosis

27. Metabolic Acidosis
• Primary AB disorder
• ↓HCO₃⁻ → ↓ pH
• Gain of strong acid
• Loss of base(HCO₃⁻)

28. ANION GAP CONCEPT
• To know if Metabolic Acidosis due to
 Loss of bicarbonate
 Accumulation of non-volatile acids
• Provides an index of the relative conc of plasma anions
other than chloride,bicarbonate
• *serum Na⁺ - (serum Cl⁻ + serum HCO₃⁻)+
• Unmeasured anions – unmeasured cations
• 8 – 16 mEq/L (5 – 11,with newer techniques)
• Mostly represent ALBUMIN

29. Concept of
Anion Gap

30. Back

31. CAUSES OF METABOLIC ACIDOSIS
(High anion gap)→(Normochloremic)
LACTIC ACIDOSIS TOXINS
KETOACIDOSIS Ethylene glycol
Diabetic Methanol
Alcoholic Salicylates
Starvation
Propylene glycol
RENAL FAILURE
(acute and chronic)

32. Normal anion gap(Hyperchloremic)
MET.ACIDOSIS causes
 Gastrointestinal  Drug-induced
bicarbonate loss hyperkalemia (with renal
A. Diarrhea insufficiency)
B. External pancreatic or small-bowel A. Potassium-sparing diuretics (amiloride,
drainage triamterene, spironolactone)
C. Ureterosigmoidostomy, jejunal B. Trimethoprim
loop, ileal loop C. Pentamidine
D. Drugs D. ACE-Is and ARBs
1. Calcium chloride (acidifying agent) E. Nonsteroidal anti-inflammatory drugs
F. Cyclosporine and tacrolimus
2. Magnesium sulfate (diarrhea)
3. Cholestyramine (bile acid diarrhea)  Other
A. Acid loads (ammonium chloride,
Renal acidosis hyperalimentation)
A. Hypokalemia B. Loss of potential bicarbonate: ketosis
1. Proximal RTA (type 2) with ketone excretion
2. Distal (classic) RTA (type 1) C. Expansion acidosis (rapid saline
administration)
B. Hyperkalemia

33. URINE NET CHARGE/UAG
Distinguish between hyperchloremic acidosis due to
DIARRHEA
RTA
UNC= Na⁺+ K⁺- Cl⁻
• Provides an estimate of urinary NH₄⁺ production
• Normal UAG = -25 to -50
Negative UAG – DIARRHEA(hyperchloremic acidosis)
Positive UAG – RTA

34. “DELTA RATIO” / “GAP-GAP”
FIG
• Ratio between ↑in AG and ↓in bicarbonate
• (Measured AG – 12):(24 – measured HCO₃⁻)
• To detect another metabolic ACID BASE disorder
along with HAGMA (nagma/met.alkalosis)
• HAGMA(NORMOCHLOREMIC ACIDOSIS) :- RATIO = 1
HYPERCHLOREMIC ACIDOSIS (NAGMA):- RATIO < 1
In DKA pts,after therapy with NS
• Met.acidosis with Met.alkalosis :- RATIO > 1
Use of NG suction and DIURETICS in met.acidosis pt

35. Compensation for Metabolic acidosis
• H+ buffered by ECF HCO3- & Hb in RBC; Plasma Pr and Pi:
negligible role (sec-min)
• Hyperventilation – to reduce PCO₂
• ↓pH sensed by central and peripheral chemoreceptors
• ↑ in ventilation starts within minutes,well advanced at 2
hours
• Maximal compensation takes 12 – 24 hours
• Expected PCO₂ calculated by
WINTERS’ FORMULA
EXP.PCO₂ =1.5 X (ACTUAL HCO₃⁻ )+8 +/- 2 mmHg
Limiting value of compensation: PCO₂ = 8-10mmHg
Quick rule of thumb :PCO₂ = last 2 digits of pH

36. Acid–Base Balance Disturbances
.
Responses to Metabolic Acidosis

37. Metabolic acidosis
 Symptoms are specific and a result of the underlying
pathology
• Respiratory effects:
 Hyperventilation
• CVS:
 ↓ myocardial contractility
 Sympathetic over activity
 Resistant to catecholamines
• CNS:
 Lethargy,disorientation,stupor,muscle twitching,COMA,
CN palsies
• Others : hyperkalemia

38. Metabolic Alkalosis
↑ pH due to ↑HCO₃⁻ or ↓acid
• Initiation process :
 ↑in serum HCO₃⁻
 Excessive secretion of net daily production of fixed
acids
• Maintenance:
 ↓HCO₃⁻ excretion or ↑ HCO₃⁻ reclamation
 Chloride depletion
 Pottasium depletion
 ECF volume depletion
 Magnesium depletion

39. CAUSES OF METABOLIC ALKALOSIS
I. Exogenous HCO3 − loads
A. Acute alkali administration
B. Milk-alkali syndrome
II. Gastrointestinal origin
1. Vomiting
2. Gastric aspiration
3. Congenital chloridorrhea
4. Villous adenoma
III. Renal origin
1. Diuretics
2. Posthypercapnic state
3. Hypercalcemia/hypoparathyroidism
4. Recovery from lactic acidosis or ketoacidosis
5. Nonreabsorbable anions including penicillin, carbenicillin
6. Mg2+ deficiency
7. K+ depletion

40. Chloride responsive alkalosis
 Low urinary chloride concentration(<15 meq/L)
Gastric acid loss
Diuretic therapy
Volume depletion
Renal compensation for hypercapnea
Chloride resistant alkalosis
 Elevated urinary chloride (>25 meq/L)
1⁰ mineralocorticoid excess
Severe pottasium depletion
 A/W volume expansion

41. Compensation for Metabolic Alkalosis
• Respiratory compensation: HYPOVENTILATION
↑PCO₂=0.6 mm  pCO2 per 1.0 mEq/L ↑HCO3-
• Maximal compensation: PCO₂ 55 – 60 mmHg
• Hypoventilation not always found due to
Hyperventilation
due to pain
due to pulmonary congestion
due to hypoxemia(PO₂ < 50mmHg)

42. Acid–Base Balance Disturbances
.
Metabolic Alkalosis

43. Metabolic Alkalosis
 Decreased myocardial contractility
 Arrythmias
 ↓ cerebral blood flow
 Confusion
 Mental obtundation
 Neuromuscular excitability
• Hypoventilation
 pulmonary micro atelectasis
 V/Q mismatch(alkalosis inhibits HPV)

44. Contraction Alkalosis
• Loss of HCO₃⁻ poor, chloride rich ECF
• Contraction of ECF volume
• Original HCO₃⁻ dissolved in smaller volume
• ↑HCO₃⁻ concentration
• Eg : Loop diuretics/Thiazides in a generalised
edematous pt.

45. Respiratory Acidosis
• ↑ PCO₂ → ↓pH
• Acute(< 24 hours)
• Chronic(>24 hours)

46. RESPIRATORY ACIDOSIS - CAUSES
CNS DEPRESSION
 DRUGS:Opiates,sedatives,anaesthetics
 OBESITY HYPOVENTILATION SYNDROME
 STROKE
NEUROMUSCULAR DISORDERS
 NEUROLOGIC:MS,POLIO,GBS,TETANUS,BOTULISM,
HIGH CORD LESIONS
 END PLATE:MG,OP POISONING,AG TOXICITY
 MUSCLE:↓K⁺,↓PO₄,MUSCULAR DYSTROPHY
AIRWAY OBSTRUCTION
 COPD,ACUTE ASPIRATION,LARYNGOSPASM

47. CONT..
CHEST WALL RESTRICTION
 PLEURAL: Effusions,
empyema,pneumothorax,fibrothorax
 CHEST WALL: Kyphoscoliosis, scleroderma,ankylosing
spondylitis,obesity
SEVERE PULMONARY RESTRICTIVE DISORDERS
 PULMONARY FIBROSIS
 PARENCHYMAL INFILTRATION: Pneumonia, edema
ABNORMAL BLOOD CO₂ TRANSPORT
 DECREASED PERFUSION: HF,cardiac arrest,PE
 SEVERE ANEMIA
 ACETAZOLAMIDE-CA Inhibition
 RED CELL ANION EXCHANGE: Loop diuretics, salicylates,
NSAID

48. Compensation in Respiratory Acidosis
Acute resp.acidosis:
 Mainly due to intracellular buffering(Hb,Pr,PO₄)
HCO₃⁻ ↑ = 1mmol for every 10 mmHg ↑ PCO₂
 Minimal increase in HCO₃⁻
 pH change = 0.008 x (40 - PaCO₂)
Chronic resp.acidosis
 Renal compensation (acidification of urine &
bicarbonate retention) comes into action
HCO₃⁻ ↑= 3.5 mmol for every 10 mm Hg ↑PCO₂
 pH change = 0.003 x (40 - PaCO₂)
 Maximal response : 3 - 4 days

49. Acid–Base Balance Disturbances
Respiratory Acid–Base Regulation.

50. • RS:
 Stimulation of ventilation ( tachypnea)
 dyspnea
• CNS:
 ↑cerebral blood flow→ ↑ICT
 CO₂ NARCOSIS
(Disorientation,confusion,headache,lethargy)
 COMA(arterial hypoxemia,↑ICT,anaesthetic effect
of ↑ PCO₂ > 100mmHg)
• CVS:
 tachycardia,bounding pulse
• Others:
 peripheral vasodilatation(warm,flushed,sweaty)

51. Post hypercapnic alkalosis
• In chronic resp.acidosis
• Renal compensation → ↑HCO₃⁻
• If the pt intubated and mechanical ventilated
• PCO₂ rapidly corrected
• Plasma HCO₃⁻ doesn’t return to normal rapidly
• HCO₃⁻ remains high

52. Respiratory Alkalosis
• Most common AB abnormality in critically ill
• ↓PCO₂ → ↑pH
• 1⁰ process : hyperventilation
• Acute: PaCO₂ ↓,pH-alkalemic
• Chronic: PaCO₂↓,pH normal / near normal

53. CAUSES OF RESPIRATORY ALKALOSIS
A. Central nervous system C. Drugs or hormones
stimulation 1. Pregnancy, progesterone
1. Pain 2. Salicylates
2. Anxiety, psychosis 3. Cardiac failure
3. Fever D. Stimulation of chest receptors
4. Cerebrovascular accident 1. Hemothorax
5. Meningitis, encephalitis 2. Flail chest
3. Cardiac failure
6. Tumor
4. Pulmonary embolism
7. Trauma
E. Miscellaneous
B. Hypoxemia or tissue 1. Septicemia
hypoxia
2. Hepatic failure
1. High altitude 3. Mechanical ventilation
2. Septicemia 4. Heat exposure
3. Hypotension 5. Recovery from metabolic
4. Severe anemia acidosis

54. Compensation for respiratory Alkalosis
Acute resp.alkalosis:
 Intracellular buffering response-slight decrease in HCO₃⁻
 Start within 10 mins ,maximal response 6 hrs
 Magnitude:2 mmol/L↓HCO₃⁻ for 10 mmHg↓PCO₂
 LIMIT: 12-20 mmol/L (avg=18)
Chronic resp.alkalosis:
 Renal compensation (acid retention,HCO₃⁻ loss)
 Starts after 6 hours, maximal response 2- 3 days
 Magnitude : 5mmol/L ↓HCO₃⁻ for 10mmHg ↓PCO₂
 LIMIT: 12-15 mmol/L HCO₃⁻

55. Acid–Base Balance Disturbances
Respiratory Acid–Base Regulation.

56. Respiratory alkalosis
• CNS:
 ↑ neuromuscular irritability(tingling,circumoral numbness)
 Tetany
 ↓ ICT(cerebral VC)
 ↓CBF(4% ↓ CBF per mmHg ↓PCO₂)
 Light headedness,confusion
• CVS:
 CO& SBP ↑ (↑ SVR,HR)
 Arrythmias
 ↓ myocardial contractility
• Others:
 Hypokalemia,hypophosphatemia
 ↓Free serum calcium
 Hyponatremia,hypochloremia

57. Acid Base Disorders
Primary disorder Compensatory response
Metabolic acidosis PCO₂=1.5 X (HCO₃⁻) + 8 +/₋ 2*Winter’s formula+
Metabolic alkalosis 0.6 mm  pCO2 per 1.0 mEq/L  HCO3-
Acute respiratory acidosis 1 mEq/L  HCO3- per 10 mm  pCO2
Chronic respiratory acidosis 3.5 mEq/L  HCO3- per 10 mm  pCO2
Acute respiratory alkalosis 2 mEq/L  HCO3- per 10 mm  pCO2
Chronic respiratory alkalosis 5 mEq/L  HCO3- per 10 mm  pCO2

58. STRONG ION APPROACH
• Metabolic parameter divided into 2 components
“STRONG” acids and bases
 Electrolytes, lactate,acetoacetate,sulfate
“WEAK” buffer molecules
 Serum proteins and phosphate
• pH calculated on the basis of 3 simple assumptions
 Total concentrations of each of the ions and acid base pairs
is known and remains unchanged
 Solution remains electroneutral
 Dissociation constants of each of the buffers are known
• Both pH and bicarbonate are dependent variables that can
be calculated from the concentrations of “STRONG” and
“WEAK” electrolytes and PCO₂

59. STRONG ION DIFFERENCE (SID)
• STRONG CATIONS – STRONG ANIONS
• Decrease in SID → Acidification of PLASMA
• Explains – NS induced ACIDOSIS
• ADV: Estimate of H⁺ conc more accurate than
Henderson Hasselbalch equation.
• DIS ADV:Complex nature of equations,increased
parameters limit clinical application

60. BASE EXCESS/DEFICIT
• Base excess and base deficit are terms applied to an
analytical method for determination of the appropriateness
of responses to disorders of acid-base metabolism
• by measuring blood pH against ambient PCO2 and against a
PCO2 of 40 mmHg
• deficit is expressed as the number of mEq of bicarbonate
needed to restore the serum bicarbonate to 25 mEq/L at a
PCO₂ of 40 mmHg compared with that at the ambient PCO₂
• misleading in chronic respiratory alkalosis or acidosis
• physiological evaluation of the patient be the mode of
analysis of acid-base disorders rather than an emphasis on
derived formulae

61. ACID BASE NORMOGRAM

62. MIXED ACID BASE DISORDER
Diagnosed by combination of clinical
assessment, application of expected compensatory
responses , assessment of the anion gap, and application
of principles of physiology.
Respiratory acidosis and alkalosis never coexist
Metabolic disorders can coexist
Eg: lactic acidosis/DKA with vomiting
Metabolic and respiratory AB disorders can coexist
Eg: salicylate poisoning (met.acidosis + resp.alkalosis)

63. THANK YOU
LIFE IS A STRUGGLE,
NOT AGAINST SIN,
NOT AGAINST MONEY POWER..
BUT AGAINST HYDROGEN IONS .
H.L.MENCKEN