Understanding

Acid-Base Physiology
& Pathology

Analysis of ABG
Dr. R. Sreedhara
Consultant Nephrologist
Fortis Hospitals, Bangalore
 Outline of presentation
• Basic chemistry principles
• pH
• Acids & Bases
• Buffering
• Henderson-Hasselbalch equation
• Clinical aspects of Acid-Base Balance
• Role of Lungs & Kidneys in AB balance
• Metabolic Acidosis & Alkalosis
• Respiratory Acidosis & Alkalosis
• The “Boston Approach” to the evaluation of
Acid-Base Disorders (5-steps)
• Clinical Case Scenarios of Acid-Base Disorders
 pH = – log [H+]
[H+] moles/L [H+] moles/L pH
0.1 10–1 1
0.01 10–2 2
0.001 10–3 3
0.0001 10–4 4
0.00001 10–5 5
pH
0.000001 10–6 6
inversely related 0.0000001 10–7 7
to
0.00000001 10–8 8
free hydrogen ion 0.000000001 10–9 9
concentration 0.0000000001 10–10 10
0.00000000001 10–11 11
0.000000000001 10–12 12
0.0000000000001 10–13 13
0.00000000000001 10–14 14
 pH in the Physiologic range
1 mmol/L = 109 nanomol/L

Relationship between
the pH and H+
concentration in the
physiologic range
 Hydrogen ion concentration
in various Body Fluid Compartments

Compartment pH H+ concentration
(nmol/L)

ECF 7.40 40

ICF 7.10 80-100

Urine 5.0 10,000

Gastric
2.0 70,000,000
fluid
 Importance of pH regulation

• Regulation of pH in a narrow range of 7.36 –

7.44 is essential for normal physiology and
normal cell metabolism and function
(enzymatic reaction and ionic concentration).

• Extreme ranges of pH (< 7.2 or > 7.55) are life

threatening due to disruption of many vital cellular
physiological processes.
 Acids and Bases
Definitions proposed by Bronsted,

Acid: A substance that can “donate” H+ ion or when

added to solution raises H+ ion (i.e., lowers pH).

Base: A substance that can “accept” H+ ion or when

added to solution lowers H+ ion (i.e., raises pH).

H2CO3 <-> H+ + HCO3–

HCl <-> H+ + Cl-

NH4+ <-> H+ + NH3

H2PO4- <-> H+ + HPO42-

ACID [HA] <-> H+ + BASE [A-]

 Daily Acid Production
• Metabolism of
Volatile Acids

carbohydrates and fats → 15,000 mmol of CO2

CO2 + water → H2CO3 (weak acid)

CO2 removed via respiration.

Non-Volatile Acids

• Noncarbonic acids derived from the metabolism of proteins.

Eg. Oxidation of sulfur-containing amino acids → H 2SO4

In typical Western diet, 1 meq/kg of non-volatile acid per

day.
15,070 mmoles = 15,070 × 106 nanomoles.
DAILY TOTAL:
Non-Volatile Acids are excreted via urine.
 At the end of the day, what would pH be if all
acid produced is retained in the body ?

pH

Initial H+
concentration
40 nanomoles/L 7.40

Daily H+
15,070 ×106 nanomoles
addition

Final H+
concentration
40 + = 358 ×106 nM/L 0.45

Nanomole = one billionth of a mole.

FATAL
 Buffering

• Buffers are chemical systems that either

accept or release H+ so that changes in
the free H+ concentration are minimized.

• Although buffers, by themselves, do not

remove acid/alkali from the body, they
shift free H+, minimizing changes in free
H+ concentration.
Buffering
 Illustration of Buffering

10 mmol/L Ketoacids produced.

Without buffering, pH would
decrease to <2.0 which is fatal.
Instantaneous buffering by Bicarbonate

Initial HCO3– = 24 mmol/L

10 mmol/L used up in buffering

ketoacids producing CO2 and water.

Final HCO3– = 14 mmol/L

With buffering, pH decreases

from 7.40 to 7.32
well within physiological range.

Note: With Insulin therapy, yet unexcreted Acetoacetate

of BHBA will be converted back to Bicarbonate.
 Physiological Buffer Systems

Extracelular buffers (40 – 45%)

1. Carbon Dioxide/Bicarbonate buffer system
2. Inorganic phosphates
3. Plasma proteins

Intracellular and Bone buffers (55 – 60%)

4. Proteins
5. Organic and inorganic phosphates
6. Hemoglobin
7. Bone
Carbon Dioxide (Carbonic Acid) – Bicarbonate
Buffer System

• By excreting volatile acids, lung regulates PaCO2.

• Is a major extracellular and open buffer system.

• In RBC, it buffers metabolic CO2.

In kidneys, it provides a substrate for acid secretion.
• It's buffering capacity is potentiated by its being an
open system allowing respiration to independently
modulate CO2.
 Law of mass action for Carbon dioxide/
bicarbonate buffer system
• The law of mass action for this reaction is
[H ] [HCO3-]
Ka 
[CO 2]dis[ H 2O]
• These relationships also can be expressed by the
Henderson-Hasselbalch equation:

[HCO3-]
pH  6.10  log
0.03 PCO2
where 6.10 is the pKa of the CO2–Bicarbonate buffer system
 INTRACELLULAR AND BONE
BUFFERS
• The primary intracellular buffers are proteins,
organic and inorganic phosphates, and, in the
erythrocyte, hemoglobin (Hb-) & plasma proteins
(Pr-):

– (Eq.) H+ + Pr- <—> HPr

– (Eq.) H+ + Hb- <—> HHb

• Above reactions, limit the rise in free hydrogen

concentration.
 Isohydric Principle
• If the H+ concentration is altered, the acid/base ratio
of all the buffers in the solution is affected.
0.03 × PCO2 [H2PO4–] [HA]
[H+] = Ka1 ————— = Ka2 ————— = Ka3 ———
[HCO3–] [HPO42–] [A-]

i.e., studying any one buffer system is adequate to

predict the behavior of all other buffer systems.

Clinically, the acid-base status of a patient is expressed in terms of

the principal extracellular buffer, the HCO3-/CO2 system:
PCO2
Henderson-
[H+] = 24 × ————
Hesselbach
[HCO3–]
equation
 Calculation of pH


HCO
pH 6.10  log 3
0.03 PaCO2

PaCO2
Henderson-
Hesselbach
equation
H  24  HCO


3
 Anion and Cation

• Anion:
An ion with negative charge
Example: Cl-, HCO3-

• Cation:
An ion with positive charge
Example: Na+, K+, Mg+
 The ultimate pH in the body will
depend on ……..

• amount of acid produced

• buffering capacity of the body

• rate of acid excretion by

– Lungs
– Kidneys
 Alveolar ventilation.
• CO2 level in blood (PaCO2) depends on
quantity of CO2 produced in the body and its
excretion by alveolar ventilation (Va).

• PaCO2 ~ CO2/Va
When CO2 production is constant, PaCO2 ~ 1/Va
High PaCO2 Alveolar
hypoventilation
Low PaCO2 Alveolar
hyperventilation
 Renal regulation of pH
• Kidneys play a predominant role in
regulating systemic bicarbonate, i.e., the
metabolic component of acid-base balance.

– Reclamation of entire filtered HCO3−

(≈ 4000 mmol of bicarbonate are filtered every day)

– Regeneration of “new” HCO3−

(to replenish bicarbonate consumed by buffering)
 Bicarbonate reclamation and
regeneration in the Kidney
• The PCT reclaims the major portion of filtered HCO3−,
lowering luminal pH from 7.3 to approximately 6.7

• The TAL and distal nephron contribute by reclaiming any

remaining HCO3− that escapes the PCT.

• Bicarbonate regeneration begins in the PCT with titration

of filtered buffers, but the key component occurs in the
collecting duct where the final urinary acidification leads
to titration of ammonia, phosphate, and other titratable
buffers. The urine pH may decrease to as low as 5.0
Bicarbonate Reabsorption in PCT & TAL
 Bicarbonate Regeneration
via Titratable Acidity

HPO42-
pH= pK + log ---------- pK for inorganic
phosphate is approx. 6.8
H PO -
Ammonium excretion in the Kidney
 Relative roles of titratable acids and
ammonia in Net Acid Excretion

• Under normal conditions,

approximately 1/3 to 1/2 of
net acid excretion is in the
form of titratable acid.

• The other 1/2 to 2/3 is the

excretion of NH4+

• Under conditions of acid

load, the capacity to
excrete NH4+ is
quantitatively much greater
than the capacity to
increase titratable acid.
Lemann J Jr., Bushinsky DA, HammLL: Bone buffering of acid and base in
humans.
Am J Physiol Renal Physiol 285: F811–F832, 2003
 Urine pH along the nephron

Fall in pH of the tubular fluid along the nephron of the rat. The major
reduction in pH occurs in the collecting tubules (the difference between the
distal tubule and ureteral urine specimens). Data from Gottschalk, CW,
Lassiter, W, William, E, Mylle, M, Am J Physiol 1960; 198:581.
 Acid base balance
• Acid base homeostasis is essential for normal
cellular enzyme function.
• Arterial pH is maintained within a very narrow range
(7.36 and 7.44) by the interteraction of

Buffering occurs within ….

1. Blood buffers ….seconds to minutes.

2. Lungs ….1 to 15 minutes.

3. Kidneys ….hours to days.

ABG Analysis
&
Interpretation
ABG analysis provides
a snapshot into the
metabolic and
respiratory processes
that maintain pH of
body fluids.
 Why learn/analyze ABG?
• Provides information on the physiological
processes that maintain pH homeostasis.

• Plays a pivotal role in diagnosis and

management of critically ill patients.

• Proper evaluation of ABG guides

appropriate diagnosis and treatment.
 An ABG Report

Parameters of importance
for evaluation of acid-base
status

Measured parameters
pCO2, pH

Calculated parameter
HCO3
 Calculation of pH


HCO
pH 6.10  log 3
0.03 PaCO2

PaCO2
Henderson-
Hesselbach
equation
H  24  HCO


3
 Terminology
• Acidemia is present when blood pH <7.35.
• Alkalemia is present when blood pH >7.45.

• Acidosis is a process which tends to acidify body

fluids (lower plasma bicarbonates) and if
unopposed will lead to a fall in pH.

• Alkalosis is a process which tends to alkalinize

body fluids (raise plasma bicarbonates) and if
unopposed will lead to a rise in pH.
 Terminology
• Metabolic
refers to disorders that result from a
primary alteration in [H+] or [HCO3-].

• Respiratory
refers to disorders that result from a
primary alteration in PCO2 due to altered
CO2 elimination.
Metabolic
Acidosis
 Metabolic Acidosis

Primary Defect: Decrease in HCO3

• Accumulation of metabolic acids (non-carbonic)
caused by:

– Excess acid production which overwhelms renal capacity

for excretion. e.g. Diabetic ketoacidosis.

– Loss of alkali:
Leaves un-neutralized acid behind. e.g. Diarrhea.

– Renal excretory failure:

Normal total acid production in face of poor renal function.
e.g. Chronic renal failure.
 Metabolic Acidosis (continued)

• Compensatory Change:

– Tissues and RBC act to increase serum HCO3 by

exchanging intracellular Na and K for extracellular
H+. Acts to raise serum HCO3− and K.

– Increased pulmonary ventilation. Fall in PCO2

brings pH back toward normal.
According to current concepts, the change in serum HCO3− concentration is
transmitted only slowly to the interstitium of the brainstem, where it signals
chemoreceptors located below the surface of the medulla oblongata. Activated
receptors translate this chemical message into a change in respiration by
signalling other neurones in the medullary respiratory centre, which in turn, alter
phrenic nerve activity and, subsequently, alveolar ventilation.
Sequential response to a H+ load, culminating in the restoration of
acid-base balance by the renal excretion of the excess H +

H+ Load

Extracellular Respiratory Intracellular Increased

buffering by compensation and bone Renal H+
HCO3 by lowering buffering excretion
PCO2

Minutes to Hours to
Immediate 2 – 4 Hours days
Hours
Buffering in metabolic acidosis
Mechanisms of buffering of
strong acid infused
intravenously in the dog.
Fifty seven percent is mediated by
cell buffers, resulting in the
movement of sodium (36 percent)
or potassium (15 percent) into the
extracellular fluid or in the
movement of chloride (6 percent)
into the cells.
Forty three percent of buffering
occurs in the extracellular fluid,
almost all by bicarbonate.

Data from Pitts, RF, Physiology of the Kidney and

Body Fluids, 3d ed, Year Book, Chicago, and from
Swan, RC, Pitts, RF, J Clin Invest 1955; 34:205.
 Causes of Metabolic Acidosis

• Acid Gain
1. L-lactic acid (= tissue hypoxia)
2. Ketoacids (= DKA, starvation)
3. D-lactic acid (= Low GI motility or altered GI
flora, eg. blind loop syndromes)
4. Intoxicants which are acids or become acids
– Methanol to formic acid
– Ethylene glycol to glyoxalic acid
– Paraldehyde to acetic acid
– Acetylsalicylic acid
– Toluene to hippuric acid Anion Gap =
5. Renal Failure Na – [Cl + HCO3]
 Causes of Metabolic Acidosis

• Loss of NaHCO3
1. Loss via GI tract (diarrhea, ileus, fistula)
2. Loss in Urine (proximal RTA, acetazolamide)
3. Failure of kidneys to make new bicarbonate
(distal RTA)
4. Acid production and the excretion of its anion in
the urine without [H+] or [NH4+] (Eg. Defective
renal reabsorption of betahydroxybutarate)
 Causes of Lactic Acidosis
• Deficit of Oxygen
– Compromised Lung function
– Comrpomised Circulatory function
– Severe anemia
• Compromised metabolism without Hypoxia
– High glycolysis due to low ATP
• Exercise, uncouplers of oxidative phosphorylation
– Defective lactic acid breakdown
• PDH deficiency (low vitamin B1, inborn errors)
• High production of ATP from fat
• Low rate of synthesis of ATP
– Low conversion of lactate to glucose
• Destruction of hepatocytes
• Defective gluconeogenesis (drugs, inborn errors)
 Metabolic Acidosis – Symptoms

• Rapid breathing
• Confusion
• Lethargy
• Cold, clammy skin
• Tachycardia and arrhythmia
 Anion Gap
• An "artefact" of how we measure blood
electrolytes
• Determined by:

Normal AG = 12
• If the anion gap is normal with acidosis then Cl-
has increased to match HCO3- decline.
• If the anion gap is increased some other anion is
involved
 Anion Gap

Unmeasured Unmeasured
Cation Anion
 High Anion Gap Metabolic Acidosis
Example: 15 millimoles of organic acid added.
15 mEq of bicarbonate will be used up while buffering.

10
 Normal Anion Gap Metabolic Acidosis
Example: 15 mEq of bicarbonate is lost.
Kidneys reclaim extra chloride to maintain electroneutrality.

10
 High Anion Gap Met. Acidosis

• Ketoacidosis
• Lactic Acidosis
• Uremia
Anion Gap = • Toxicity
(Na – HCO3 – Cl) – Salicylate
– Ethylene Glycol
– Methanol
– Paraldehyde
• Massive rhabdomyolysis
 Renal Tubular Acidosis
Type I Type II Type IV

Location Distal Proximal Distal

Defect Distal Diminished Aldosterone

acidification HCO3 deficiency or
resorption resistance

Urine pH > 6.0 Variable Usually < 5.3

Plasma Low or Low or High

K+ normal normal
Plasma Very low Moderately Usually >15
HCO3 (may be < 10 low (14-20)
mEq/L)
 Causes of RTAs

• Type I RTA:
– primary, amphotericin, Sjogren’s, myeloma, marked
volume depletion.

• Type II RTA:
– primary, myeloma, acetazolamide, heavy metals (Pb,
Cd, Hg, others), Fanconi syndrome.

• Type IV RTA:
– most commonly diabetes mellitus.
– Also commonly caused by heparin, Addison's
disease, NSAIDs, etc. The main problem here is
hyperkalemia and not acidosis.
 Base Excess
• An index to quantify the metabolic (non-
respiratory) component of acid-base balance.

• It is defined as the amount of acid or base (in mmol/L) to

be added in vitro to 1 liter of fully oxygenated blood in
order to return the pH to 7.4 in the setting of a normal
PaCO2 at 37°C.

cBase(ecf) = 16.2 × (pH – 7.40) – 24.8 + cHCO3–

• The use of base excess is not well established.

 Base Excess
• An empirical expression that approximates the
amount of acid or base required to titrate one
liter of blood back to a normal pH of 7.40

• It allows the estimation of the number of

equivalents of sodium-bicarbonate or ammonium
chloride required to correct the patient’s pH to
normal.
 Base Excess
• Base Excess of ECF [BE(ecf)]
– Formerly known as In vivo base excess
– Reflects only the non-respiratory component
of pH disturbances

• Base Excess of Blood [BE(B)]

– Formerly known as In vitro base excess
– Reflects non-respiratory and respiratory
components of pH disturbances
Pattern of Changes in Acid-Base Disorders

Primary Initial Compensatory

disorder change change

Metabolic ↓ HCO3 ↓ PCO2

acidosis
Metabolic
Alkalosis
 Metabolic Alkalosis

Primary Defect: Rise in HCO3

• from renal or extra-renal sources.

• Compensatory change:
– Tissues and RBC exchange intracellular H+
for extra-cellular Na+ and K+
– Hypoventilation and elevation of PaCO2
(Maximal PaCO2 rarely exceeds 55 mmHg)
Pattern of Changes in Acid-Base Disorders

Primary Initial Compensatory

disorder change change

Metabolic ↓ HCO3 ↓ PCO2

acidosis

Metabolic ↑ HCO3 ↑ PCO2

alkalosis
 Metabolic Alkalosis – Pathogenesis

Generation
• Loss of hydrogen ion from upper GI tract
(vomiting) or urine (diuretics)
• Addition of alkali – administration of bicarbonate
or its precursors (citrate, lactate, etc.)
Maintenance
• Volume/chloride depletion
• Hypokalemia
• Aldosterone excess
 Metabolic Alkalosis – Causes

Saline Responsive Saline Resistant

Urine Chloride (<10 mEq/L) Urine Chloride (>20 mEq/L)

ECF Volume Depletion Hypertensive (Normal

Vomiting/Gastric Suction or increased ECF)
Diuretics Hyperaldosteronism
Hypercapnia correction Cushing syndrome

No ECF Vol. Depletion Normo/Hypotensive

NaHCO3 infusion Bartter’s syndrome
Multiple transfusions Severe K depletion
 Metabolic Alkalosis – Clinical Features
pH >7.65 = 80% mortality
• CNS:
– Increased neuromuscular excitability leading to
paresthesia, light headache, and carpopedal spasm
• CVS:
– Hypotension, cardiac arrhythmias
• Other:
– Weakness, muscle cramps, postural dizziness
– Muscle weakness and polyuria due to hypokalemia
• Respiratory:
– Compensatory hypoventilation may lead to hypoxia
symptoms in patients with pre-existing lung disease
 D/D of Metabolic Alkalosis
Urine Saline Saline
Electrolyte Sensitive Resistant

Cl < 10 mEq/L > 20 mEq/L

(unless on diuretics)

Na < 20 mEq/L > 20 mEq/L

(unless recent vomiting)

K May be high if Usually high as

high distal Na aldosterone is
(diuretics or recent
vomiting)
acting
 Metabolic Alkalosis – Treatment
• Treat underlying cause
• Saline reponsive
– Normal saline with KCl or Isolyte-G
– H2 inhibitors or PPI
– In diuretic induced, dose reduction, KCl
suplementation, spironolactone
– Discontinue exogenous sources of alkali (bicarbonate,
RL, acetate, citrate)
– When pH > 7.65, may administer 0.1 N HCl via
central veins
– Dialysis
• Saline Resistant – Treat the cause.
Spironolactone, K correction and Na restriction.
 Simple metabolic alkalosis

• Most common acid base disorder in

hospitalised patients.
• pH >7.65 associated with up to 80% mortality.
• Occurs only in the presence of one of the
bicarbonate retaining mechanisms.
– Chloride depletion
– Potassium depletion (+/- hypertension)
– Base loading (multiple blood transfusions).
Simple metabolic alkalosis (contd.)

• Base loading needs no specific treatment.

• Hydrochloric acid is administered when there
is an immediate need for correction of pH.
– In case of CNS effects, cardiac arrhythmia, hepatic
encephalopathy, pH > 7.6.
• H2 receptor blockers in case of prolonged
vomiting in order to reduce H+ loss
Respiratory
Acidosis
 Respiratory Acidosis

Primary Defect: Rise in PCO2

• Decrease in pulmonary clearance of CO2

• Compensatory Change:
– Acute (<24 hrs): Buffering by tissue and RBC to
increase HCO3. Rarely more than 4 mEq

– Chronic (>72 hrs): Stimulation of renal tubular

secretion of H+ thus synthesizing more HCO3.
Chloride is lost along with NH4+
Response to an increase in PCO2

Increased PCO2

Intracellular Increased
Buffering Renal H+
Excretion

10 to 30
minutes Hours to Days
 Respiratory Acidosis – Causes
• CNS Depression
– Drugs (anaesthesia, sedatives), infection, stroke
• Neuromuscular impairment
– Myopathy, Myasthenia gravis, polymyositis, hypokalemia
• Ventilation restriction
– Rib fracture, pneumothorax, hemothorax
• Airway
– Asthma, obstruction
• Alveolar diseases
– COPD, pulmonary edema, ARDS, pneumonitis
• Miscellaneous
– Obesity, Hypoventilation
Respiratory Acidosis – Symptoms
• Headache
• Anxiety
• Blurred vision
• Restlessness
• Drowsiness
• Tremors
• Delirium
• Coma
Buffering in respiratory acidosis
Mechanisms of buffering of
CO2 in respiratory acidosis
in the dog.

Virtually all buffering occurs

within the cells, 37 percent in
exchange for sodium, 14 percent
in exchange for potassium, and
29 percent via chloride entry into
cells. The source of
approximately 11 percent of the
buffering has not been identified.

Data from Pitts, RF, Physiology of the Kidney

and Body Fluids, 3d ed, Year Book, Chicago,
and from Giebisch, G, Berger, L, Pitts, RF, J Clin
Invest, 34:231, 1955.
 Respiratory Acidosis – Treatment
• Acute
– Treat the cause.
– Bronchodilators.
– Mechanical ventilation.
– Antibiotics
• Chronic
– Oxygen -long term supplemental.
– Nasal continuous positive airway pressure.
– Improving respiratory muscle function.
– Drugs- Progesterone, Doxapram, Almitrine,
Acetazolamide, Methyphenidate and Caffeine.
Respiratory
Alkalosis
 Respiratory Alkalosis

Primary Defect: Decrease in PCO2

• Compensatory Change:
– Acute (<24 hrs): Buffering by tissue and RBC
to lower HCO3. Rarely to less than 18 mEq/L

– Chronic (>72 hrs): Impairs kidney's ability to

excrete acid thus lowering HCO3. If more than
2 weeks, pH may return to normal.
 Respiratory Alkalosis – Causes
• Hypoxemia
– Pneumonia, interstitial diseases, pulm emboli, edema, etc.
– CHF
– Severe anemia
– High altitude resisdence
• Direct stimulation of the medullary respiratory center
– Psychogenic/voluntary
– Pain
– Pregnacy
– Hepatic failure
– Gram Negative sepsis
– Salicylate toxicity
– Rapid correction of metabolic acidosis
– Neurological – CVA, trauma, tumors, infections, etc.
• Mechanical Ventilation (overtreatment)
Respiratory Alkalosis – Symtpoms
• Diziness
• Peripheral paraesthesia
• Confusion
• Dry mouth
• Bloating
Respiratory Alkalosis – Treatment
• Treat the cause
• Does not need treatment unless pH > 7.50
• Relief of hypoxia.
• Rebreathing into a non compliant bag as
long as hyperventilation exists.
• Treatment of anxiety.
Pattern of Changes in Acid-Base Disorders

Primary Initial Compensatory

disorder change change

Metabolic ↓ HCO3 ↓ PCO2

acidosis

Metabolic ↑ HCO3 ↑ PCO2

alkalosis

Respiratory ↑ PCO2 ↑ HCO3

acidosis

Respiratory ↓ PCO2 ↓ HCO3

alkalosis
Dictums in ABG Analysis (1)

 Primary change &

Compensatory change
always occur in the
same direction.
The Boston Approach

to evaluation of

Acid-Base Disorders
 5-Steps in the Evaluation of
Systemic Acid Base Disorders

1. Comprehensive history and physical examination.

2. Evaluate simultaneously performed ABG & serum
electrolytes.
3. Identification of the dominant disorder.
4. Calculation of compensation.
5. Calculate the anion gap and the Δs.
1. Anion Gap
2. Δ AG
3. Δ Bicarbonate
Dictums in ABG Analysis (2)

 pH and Primary parameter

change in the same
direction suggests a
metabolic problem
Dictums in ABG Analysis (2)

 pH and Primary parameter

change in the same
direction suggests a
metabolic problem

 pH and Primary parameter

change in the opposite
direction suggests a
Step 3: Identification of the dominant disorder

same direction
pH and Primary Metabolic problem
parameter
change opposite direction
Respiratory problem
Step 4. Check if the compensatory
response is appropriate or not.

If the compensation is not

appropriate, suspect a second
(and perhaps a triple) acid-
base disorder.
 What is the
Magnitude of
Compensation?
 Step 4:
Calculation of compensation
Mean "whole body" response equations for simple acid-base disturbances.
Disorder pH Primary Compensatory Equation
change Response
Metabolic   [HCO3-]  PCO2 ΔPCO2  1.2  ΔHCO3
Acidosis
Metabolic   [HCO3-]  PCO2 ΔPCO2  0.7  ΔHCO3
Alkalosis
Respiratory   PCO2  [HCO3-] Acute:
Acidosis ΔHCO3  0.1  ΔPCO2
-

Chronic:
ΔHCO3  0.3  ΔPCO2
-

Respiratory   PCO2  [HCO3-] Acute:

Alkalosis ΔHCO3  0.2  ΔPCO2
-

Chronic:
ΔHCO3  0.5  ΔPCO2
-

Note: The formula calculates the change in the compensatory parameter.

 Compensation Formula Simplified

Acidosis 1.2
Metabolic
Alkalosis 0.7

Acidosis 0.1 0.3

Respiratory
Alkalosis 0.2 0.5
Acute Chronic
 Magnitude of Compensation
Primary Compensatory Comp. Factor x Primary
change
disorder change

Metabolic ↓ PaCO2 1.2  ↓ HCO3

acidosis
Metabolic ↑ PaCO2 0.7  ↑ HCO3
alkalosis
Respiratory ↑ HCO3 0.1  ↑ PaCO2
acidosis 0.3 
Respiratory ↓ HCO3 0.2  ↓ PaCO2
alkalosis 0.5 
 Step 5: Calculate the “gaps”

Anion gap = Na+ − [Cl− +

HCO3−]
Δ AG = Anion gap − 12

Δ HCO3 = 24 − HCO3

Add Δ AG to measured HCO3− to obtain

 Delta _ AG 
bicarbonate level that would have existed   Pr e _ existing _ Bicarb
 
IF  Current _ Bicarb
the high AG metabolic acidosis were to be
absent, i.e., “Pre-existing Bicarbonate.”
Dictums in ABG Analysis (3)

 Renal and pulmonary

compensatory mechanisms
return pH toward but rarely
to normal.

Corollary:
A normal pH in the presence
of changes in PCO2 or HCO3
suggets a mixed acid-base
 Common clinical states and associated acid-base disorders
Clinical state Acid-base disorder
Renal failure Metabolic acidosis

Vomiting Metabolic alkalosis

Severe diarrhea Metabolic acidosis

Cirrhosis Respiratory alkalosis

Hypotension Metabolic acidosis

COPD Respiratory acidosis

Sepsis Respiratory alkalosis, metabolic acidosis

Pulmonary embolus Respiratory alkalosis

Pregnancy Respiratory alkalosis

Diuretic use Metabolic alkalosis

 Clues to Mixed Acid-Base Disorders

• Normal pH (with the exception of chronic

respiratory alkalosis)

• PCO2 and HCO3 deviating in opposite

directions

• pH change in the opposite direction of a

known primary (dominant) acid-base
disorder
 Calculation of pH


HCO
pH 6.10  log 3
0.03 PaCO2

PaCO2
Henderson-
Hesselbach
equation
H  24  HCO


3
Acid-base nomogram

Shown are the

90% confidence limits
(range of values) of the
normal respiratory and
metabolic compensations
for primary acid-base
disturbances. (From
DuBose)
Clinical Case Scenarios of
Acid-Base Disorders
 Precautions in arterial sampling

• Steady state of ventilatory parameters.

– If no pulmonary disease – steady state reached in 10 minutes.
– If pulmonary disease – steady state reached in 20 – 30
minutes.

• Anaeroic collection

• Avoid excess heparin

– may in itself reduce pH; 0.05 ml of heparin per 1 ml of blood
(<1:20)

• No delay in processing (or cool to 4°C)

– Can be refrigerated for a maximum of 2 hrs.
 Case 1
• A 15 yr old juvenile diabetic presents with abdominal
pain, vomiting, fever & tiredness for 1 day. He had
stopped taking insulin 3 days ago. Examination
revealed tachycardia, BP- 100/60, signs of
dehydration. Abdominal examination was normal.

• ABG:
pH 7.31 Serum Electrolytes:
PaCO2 26 mmHg Na 140 mEq/L
HCO3 12 mEq/L K 5.0 mEq/L
PaO2 92 mm Hg Cl 100 mEq/L

• Evaluate the acid-base disturbance(s)?

 Case 1: Solution
• Dominant disorder is Metabolic Acidosis
• Compensation formula:
pH 7.31
Δ PaCO2 = 1.2 × Δ HCO3 PaCO2 26
HCO3 12
= 1.2 × 12 PaO2 92
= 14.4
Na 140
PaCO2 = 40 – 14 = 26 K 5.0
Compensation is appropriate. Cl 100

• Anion Gap = 140 – (100 + 12)

= 28
AG is high.
 Case 1: Solution
• Δ AG = 28 – 12 pH 7.31
= 16 PaCO2 26
HCO3 12
PaO2 92
• Add Δ AG to existing HCO3
Na 140
= 12 + 16 K 5.0
Cl 100
= 28

Pre-existing Bicarbonate value IF the High AG producing

acidosis did not occur.
(Likely scenarios: Metabolic Alkalosis or Respiratory Acidosis)

High AG Met. Acidosis + Met. Alkalosis

 Case 2
• A 24 yr old boy presents with continuous vomiting of
3 days duration, mental confusion, giddiness, and
tiredness for 1 day.
• Examination revealed tachycardia, hypotension and
dehydration.
• ABG
pH 7.50 Serum Electrolytes:
PaCO2 48 Na 139
HCO3 32 K 3.9
PaO2 90 Cl 85

• Evaluate the acid-base disturbance(s)?

 Case 2: Solution
• Dominant disorder is Metabolic Alkalosis
• Compensation formula:
pH 7.50
Δ PaCO2 = 0.7 × Δ HCO3 PaCO 2 48
HCO 32
= 0.7 × 8 PaO
3
90
2
= 5.6
Na 139
PaCO2 = 40 + 6 = 46 K 3.9
Compensation is appropriate. Cl 85

• Anion Gap = 139 – (85 + 32)

= 22
AG is high.
 Case 2: Solution
• Δ AG = 22 – 12
= 10 pH 7.50
PaCO2 48
• High AG metabolic acidosis HCO3 32
PaO2 90

If this High AG metabolic acidosis Na 139

were not present, then the pre-existing K 3.9
Bicarbonate would have been Cl 85

32 + 10 = 42

Metabolic Alkalosis + High AG Met. Acidosis

 Case 3: Varieties of Metabolic Acidosis

Patient A B C
ECF volume Low Low Normal
Glucose 600 120 120
pH 7.20 7.20 7.20
Na 140 140 140
Cl 103 118 118
HCO3- 10 10 10
AG 27 12 12
Ketones 4+ 0 0
High-AG Non-AG Non-AG
Met. Met. Met.
Acidosis Acidosis Acidosis
 Renal handling of Hydrogen in
Metabolic Acidosis
• In the setting of metabolic acidosis, normal kidneys try to
increase H+ excretion by increasing titratable acidity and
ammonia. The latter is excreted as NH4+.

• When NH4+ is excreted, it also causes increased chloride loss,

to maintain electrical neutrality.

• Chloride loss, therefore, will be in excess of Na and K.

• Urine Anion-Gap = Na + K – Cl

• In metabolic acidosis, if Urine anion gap is negative, it

suggests that the kidneys are excreting H+ effectively.
Urine Electrolytes in Metabolic Acidosis

Patient A B C
U. Na 10 50
U. K 14 47
U. Cl 74 28
Urine AG –50 +69
Dx: Diarrhea RTA

Urine Anion Gap = (U. Na + U. K – U. Cl)

In Normal anion gap Metabolic Acidosis,
Positive Urine AG suggests distal Renal Tubular Acidosis

Negative Urine AG suggests non-renal cause for Metabolic

Acidosis.
 Case 4
• A 50 yr old man presented with history of
progressive dyspnoea with wheezing for 4 days.
• He also had fever, cough with yellowish
expectoration.
• He had increased sleepiness for 1 day.
• On examination, he was tachypnoeic, pulse-
100/min bounding, BP-160/96, central cyanosis +,
drowsy, asterixis +, RS – B/L extensive wheezing +.
• CXR- hyperinflated lung fields with tubular heart.
 Case 4: Laboratory data
• ABG:
pH 7.30
PaCO 60 mmHg
2

HCO 28 mEq/L
3

PaO 68 mm Hg
2

• Serum Electrolytes:
Na 136 mEq/L
K 4.5 mEq/L
Cl 98 mEq/L
• Evaluate the acid-base disturbance(s)?
 Case 4: Solution
• Dominant disorder is Respiratory Acidosis
• Compensation formula:
pH 7.30
Δ HCO3 = 0.3 × Δ PaCO2 PaCO 2 60
HCO 28
= 0.3 × 20 PaO
3
68
2
=6
Na 136
HCO3 = 24 + 6 = 30 K 4.5
Cl 98
Compensation is appropriate.
• Anion Gap = 138 – (98 + 28)
= 10
AG is normal.
 Case 5
• 20 year old girl presented with complaints of
difficulty in breathing and upper abdominal
discomfort for the past 1 hr.

• On examination, vitals normal, patient

hyperventilating, RS – normal, Abdomen – normal.
 Case 5: Laboratory data
• ABG:
pH 7.50
PaCO 25 mmHg
2

HCO 21 mEq/L
3

PaO 100 mm Hg
2

• Serum Electrolytes:
Na 137 mEq/L
K 3.9 mEq/L
Cl 99 mEq/L
Calcium 9.0 mEq/L
• Evaluate the acid-base disturbance(s)?
 Case 5: Solution
• Dominant disorder is Respiratory Alkalosis
• Compensation formula:
pH 7.50
Δ HCO3 = 0.2 × Δ PaCO2 PaCO 25 2
= 0.2 × 15 HCO 3 21
=3 PaO 2 100

HCO3 = 24 – 3 = 21 Na 137
Compensation is appropriate. K
Cl
3.9
99
• Anion Gap = 137 – (99 + 21) Calcium 9.0
= 17
AG is slightly high which can be seen in
respiratory alkalosis.
 Case 6
For each of the following sets of arterial blood gas
values, what is (are) the likely acid-base disorder(s)?

pH PaCO2 HCO3 Acid-Base status

respiratory acidosis and
7.28 50 23 metabolic acidosis
respiratory alkalosis and
7.50 33 25 metabolic alkalosis
metabolic acidosis and
7.23 34 14 respiratory acidosis
 Case 7
• Explain the acid-base status of a 35-year-old man
with history of chronic renal failure treated with high
dose diuretics admitted to hospital with pneumonia
and the following lab values:
ABG Serum Electrolytes
pH 7.52 Na+ 145 mEq/L
PaCO2 30 mm Hg K+ 2.9 mEq/L
PaO2 62 mm Hg -
Cl 98 mEq/L
-
HCO 21 mEq/L
3
 Case 7: Solution
• Dominant disorder is Respiratory Alkalosis
• Compensation formula:
pH 7.52
Δ HCO3 = 0.2 × Δ PaCO2 PaCO 2 30
= 0.2 × 10 HCO3 21
=2 PaO
2 62

HCO3 = 24 – 2 = 22 Na 145
Compensation is appropriate. K
Cl
2.9
98
• Anion Gap = 145 – (98 + 21)
= 26
AG is very high suggestive of metabolic
acidosis.
 Case 7: Solution
• Δ AG = 26 – 12
= 14
pH 7.52
If this High AG metabolic acidosis PaCO2 30
were not present, then the pre-existing HCO3 21
Bicarbonate would have been PaO2 62
21 + 14 = 35
Na 145
K 2.9
Cl 98

Respiratory Alkalosis +
High AG Metabolic Acidosis +
Metabolic Alkalosis
 Case 8
• The following values are found in a 65-year-old
patient. Evaluate this patient's acid-base status?
ABG Serum Chemistry
pH 7.51 Na + 155 mEq/L
PaCO2 50 mm Hg K+ 5.5 mEq/L
HCO3- 39 mEq/L Cl- 90 mEq/L
CO2 40 mEq/L
BUN 121 mg/dl
Glucose 77 mg/dl
 Case 8: Solution
• Dominant disorder is Metabolic Alkalosis
• Compensation formula:
Δ PaCO2 = 0.7 × Δ HCO3 pH 7.51
= 0.7 × 16 PaCO 2 50
HCO 40
= 11.2 PaO
3
62
PaCO2 = 40 + 11 = 51 2

Compensation is appropriate. Na
K
155
5.5
Cl 90
• Anion Gap = 155 – (90 + 40) BUN 121

= 25
AG is high.
 Case 8: Solution
• Δ AG = 25 – 12
= 13 pH 7.51
• High AG metabolic acidosis PaCO2
HCO3
50
40
PaO2 62
If this High AG metabolic acidosis
Na 155
were not present, then the pre-existing K 5.5
Bicarbonate would have been Cl 90
BUN 121
40 + 13 = 53

Metabolic Alkalosis +
High AG Metabolic Acidosis
 Case 9
• A 52-year-old woman has been mechanically ventilated for
two days following a drug overdose. Her arterial blood gas
values and electrolytes, stable for the past 12 hours, show:

ABG Serum Chemistry

pH 7.45 Na + 142 mEq/L
PaCO2 25 mm Hg K+ 4.0 mEq/L
Cl- 100 mEq/L
HCO3- 18 mEq/L
 Case 9: Solution
• Dominant disorder is Chronic Respiratory
Alkalosis
• Compensation formula: pH 7.45
PaCO 25
Δ HCO3 = 0.5 × Δ PaCO2 HCO
2
18
= 0.5 × 15 3

= 7.5 Na 142
HCO3 = 24 – 8 = 16 K 4.0
Cl 100
Compensation is appropriate.
• Anion Gap = 142 – (100 + 18)
= 24
AG is very high suggestive of metabolic
acidosis.
 Case 9: Solution
• Δ AG = 24 – 12
= 12
pH 7.45
If this High AG metabolic acidosis PaCO2 25
were not present, then the pre-existing HCO3 18
Bicarbonate would have been
Na 142
18 + 12 = 30 K 4.0
Cl 100
Indicates presence of Metabolic Alkalosis.

Chronic Respiratory Alkalosis +

High AG Metabolic Acidosis +
Metabolic Alkalosis
 Case 10
• An 18-year-old college student is admitted to the ICU for an
acute asthma attack, after not responding to treatment
received in the Casualty department. ABG values (on room
air) show: pH 7.46, PaCO2 25 mm Hg, HCO3- 17 mEq/L,
PaO2 55 mm Hg, SaO2 87%. Her peak expiratory flow rate
is 95 L/min (25% of predicted value).

• Asthma medication is continued. Two hours later she

becomes more tired and peak flow is < 60 L/minute. Blood
gas values (on 40% oxygen) now show: pH 7.20, PaCO2 52
mm Hg, HCO3- 20 mEq/L, PaO2 65 mm Hg. At this point
intubation and mechanical ventilation are considered. What
is her acid-base status?
 Case 10 Solution
• Initial status:
– chronic respiratory alkalosis, resulting from several
days of hyperventilation (pH almost normal)

• When her asthamatic condition has worsened,

she has acutely hypoventilated.

• The second set of blood gas values reflects

acute respiratory acidosis on top of a chronic
respiratory alkalosis.
 Case 11
• A 21 year old male with progressive renal insufficiency is
admitted with abdominal cramping. He had congenital
obstructive uropathy with creation of ileal loop for diversion.
On admission,

ABG Serum Chemistry

pH 7.20 Na + 140 mEq/L
PaCO2 24 mm Hg K+ 5.6 mEq/L
Cl- 110 mEq/L
HCO3- 10 mEq/L
 Case 11: Solution
• Dominant disorder is Metabolic Acidosis

• Compensation formula: pH 7.20

PaCO2 24
Δ PaCO2 = 1.2 × Δ HCO3 HCO3 10
= 1.2 × 14
= 16.8 Na 140
K 5.6
PaCO2 = 40 – 17 = 23 Cl 110
Compensation is appropriate.
• Anion Gap = 140 – (110 + 10)
= 20
High anion-gap metabolic acidosis.
 Case 11: Solution
• Δ AG = 20 – 12 pH 7.20
PaCO2 24
=8 HCO3 10

If this High AG metabolic acidosis Na 140

were not present, then the pre-existing K 5.6
Cl 110
Bicarbonate would have been
10 + 8 = 18
i.e., presence of a condition with a low Bicarbonate even
before the onset of High AG Met. Acidosis 
Normal AG Metabolic Acidosis.
High AG Met Acidosis + Normal-AG Met. Acidosis
Mixed Metabolic Acidosis
 Case 12
• A 45 year old female with Parameter Initial
Subseq
hypertension was treated uent
with low salt diet and
diuretics. BP 135/85. Na 137 138
Otherwise normal.
See initial lab values. K+ 3.1 2.8
• She developed profound Cl- 90 102
water diarrhea, nausea and
weakness. HCO3 35 25
• On exam, HR = 96, T=100.6 pH 7.51 7.42
F, BP 115/70. Abdominal
tenderness with guarding on PaCO2 47 39
palpation.
 Case 12: Solution
• Initally, dominant disorder is Metabolic Alkalosis

• Compensation formula: pH 7.51

Δ PaCO2 = 0.7 × Δ HCO3 PaCO2 47
= 0.7 × 11 HCO3 35
= 7.7
Na 137
PaCO2 = 40 + 8 = 48 K 3.1
Compensation is appropriate. Cl 90

• Anion Gap = 137 – (90 + 35)

= 12
AG is normal.
 Case 12: Solution
• Subsequently, she has developed
pH HCO3 PaCO2
↓ ↓ ↓

pH 7.51  7.42
PaCO2 47  39
HCO3 35  25

Na 137  138
K 3.1  2.8
Cl 90  102
 Case 12: Solution
• Subsequently, she has developed
pH HCO3 PaCO2
↓ ↓ ↓ Metabolic acidosis

The decrease in bicarbonate is almost same as

the rise in chloride.
• Final Diagnosis:
Metabolic Alkalosis +
Hyperchloremic (non-AG) Metabolic Acidosis
 Case 13
• A patient with salicylate overdose.
pH = 7.45
PCO2 = 20 mmHg
HCO3 = 13 mEq/L

• Dominant disorder: Respiratory alkalosis

• Appropriate Compensation would have been
HCO3 of 20 (24 – 4)

• Lower than expected HCO3 suggests presence of

metabolic acidosis as well.
 Case 14
• A 55 year old female with DM Nephropathy was admitted
with acute LV failure and hyperkalemia. ST-T changes and
increased troponin noted.
• Hemodialysis was initiated.
• CAG revealed near normal coronaries.
• She was about to be discharged home when she developed
sudden cardiorespiratory arrest.
• CPR and ACLS begun and after about 8 mins cardiac
rhythm returned.
• She was transferred to ICU and placed on ventilator at
about 1 PM.
 Case 14 (continued): ABG & Ventilator settings
Parameter 1 PM 2 PM 6 PM 8 PM
pH 6.99 7.24 7.52 7.54

PO2 162 73 274 131

PaCO2 49 33 17 20
HCO3 12 14 13 16
Base Excess –20 –12 –6 –3
Ventilator settings
Mode CMV CMV CMV CMV
Rate 20 20 20 16
Tidal volume 400 400 500 500
FIO2 100% 80% 80% 60%
Sod. Bicarb Increase Decrease Decr. Rate &
Action Taken
3 amps. Tidal vol. Rate Ch. To SIMV
 Case 15
• 64 yr male with DM underwent CABG.
• Post-surg changes,
– Hemodynamically stable
– Patient was polyuric.
– pH decreased from 7.34 to 7.22  7.15 over 18 hours.
– Bicarbonate 20  8
– Serum glucose within normal range, did not receive
insulin.
– Lactates within normal range.
– Serum cortisol very high (55).
• Serial ABGs shown
Case 15 – POD # 0
Case 15 – POD #1
Case 15 – POD #2
Case 15 - Diagnosis

Euglycemic Keto-
Acidosis due to SGLT-2
Inhibitor.
Euglycemic DKA with SGLT2 Inhibitors
Thank you!