Acid-Base Disorders

HBMLS 4 2019
D. VHANDA
Goals
 Learn to work through acid-base disorders
 Be able to recognize and work through multiple offsetting
disorders that are coincident in the same patient
 Understand the basic biochemistry and physiology of
acid-base balance.
 Understand human acid-base balance and interpret
clinical acid-base data.
 Understand the diseases that cause acid-base
disturbance
Acid Base Disturbances

What is it ?

changes in arterial PCO2, HCO3 & pH.

Maintaining Acid-Base Balance
Controlled by the Lungs, Kidneys and Buffers
Disrupted by Vomiting, Diarrhea, Respiratory Failure,
Kidney Failure, Infections and Ingestions
Body pH
• must be maintained within very narrow limits
• most body systems function optimally at a pH of near 7.4
• many reactions in the body dependent on enzymes
• enzymes function maximally within a narrow pH range
• If the degree of deviation from normal pH is great enough
 enzymes cease to function
 nerve and muscle activity weakens
 metabolic activities become deranged
 life CEASES
 Normal blood PH : 7.35-7.45
 Maintenance of blood pH -
important homeostatic mechanism of the
body.

pH affects all functional proteins and

biochemical reactions, so closely regulated

 PH <7.35 leads to Acidosis or

acidemia Caused by accumulation of acids or by a
loss of bases

pH >7.45 leads to Alkalosis or alkalemia. Occurs

when bases accumulate or acids are lost
Metabolic Disorders

Processes that directly alter bicarbonate

concentration
Metabolic acidosis: decreased bicarbonate
Metabolic alkalosis: increased bicarbonate
Respiratory Disorders
Processes that directly alter CO2
Respiratory acidosis: increased CO2
Respiratory alkalosis: decreased CO2
Buffer effect: slightly increased HCO3 with respiratory
acidosis. Slightly decreased HCO3 with respiratory
alkalosis.
 Respiratory Regulation of Acid Base Balance-

ALVEOLAR
H+ VENTILATION PaCO2

ALVEOLAR
H+ VENTILATION PaCO2
Terms and Definitions
Variable Primary Normal Range, Primary
Disorder arterial Gas Disorder
pH Acidemia 7.35 - 7.45 Alkalemia
pCO2 Respiratory 35 - 45 Respiratory
alkalosis acidosis
HCO3 Metabolic 22 – 26 Metabolic
acidosis Alkalosis
Respiratory compensation for metabolic disorders is
rapid
Full metabolic compensation for respiratory
disturbances requires renal adjustment and takes 3-5
days
Buffering
Prevent wide changes in pH in response to the
addition of base or acid
Bicarbonate is the major extracellular buffer (can be
easily measured)
There are also intracellular buffers
The presence of buffers reduces changes in pH in
response to acid-base disorders.
Immediate onset
Purpose of Acid-Base Balance
•Maintain normal pH by buffer systems

Buffer Pair H+ Acceptor H+ Donor

Bicarbonate HCO3- H2CO3

(ECFV)
Phosphate H2PO42- H2PO4
(urine)
Ammonia (urine) NH3 NH4+

Protein Protein Protein

Secondary(Compensatory) Mechanisms
In addition to buffering mechanisms, additional
secondary (compensatory) physiologic responses occur
in response to changes in pH.
Invariably present in simple acid-base disorders (if not
present, it is a mixed disorder)
Compensatory mechanisms
The respiratory system compensates for metabolic
disorders by altering CO2 (via the lungs, rapid onset,
minutes)
Compensation for respiratory disorders occurs by
alterations in bicarbonate concentration (via the kidney,
slower onset 1-2 days)
 Respiratory Mechanisms

• Arterial PCO2 stimulates chemoreceptors in the medulla

oblongata
• An elevated arterial blood PCO2 is a stimulus to
increase ventilation leading to increased expiration of
CO2 hence increase blood pH
• Conversely, a drop in blood PCO2 inhibits ventilation;
the consequent rise in blood [H2CO3] reduces the
alkaline shift in blood pH
 Renal Mechanisms

• Ca n eliminate large amounts of acid

• Ca n also excrete base
• Ca n conserve and produce bicarb ions
• Most effective regulator of pH
• If kidneys fail, pH balance fails
23
Mechanisms that Buffer an Acid Load

Buffer systems Extracellular Immediate

(primarily bicarbonate) fluid (HCO3- + H+ ↔ H2CO3 ↔ CO2
+ H20)

Increased rate and Lungs Minutes to hours

depth of breathing to
decrease CO2

Buffer systems Intracellular 2-4 hours

(phosphate, fluid
bicarbonate, protein)

Hydrogen ion excretion, Kidneys Hours to days

bicarb reabsorption, &
bicarb generation
Summary
Disorder pH HCO3- pCO2 Comment

Metabolic ↓ ↓ (primary) ↓(compensatory) All 3 markers

acidosis go in same
direction

Metabolic (primary) (compensatory) All 3 markers

alkalosis go in same
direction

Resp. ↓ (compensatory) (primary) pH goes opp.

acidosis other 2 markers

Resp. ↓ (compensatory) ↓ (primary) pH goes opp.

alkalosis other 2 markers
 Diagnosis of acid Base Disorder

1. Determine the primary disturbance:

– Acidemia or Alkalemia: look at the pH
< 7.40 = acidemia
> 7.40 = alkalemia
– Respiratory or Metabolic: look at HCO3 and CO2
HCO3 = primary metabolic acidosis
pCO2 = primary respiratory acidosis
and vice versa for alkalosis
 Diagnosis of acid Base Disorder

2. Determine acute or chronic for Respiratory

Disturbance:
o Compensation attempts to normalize pH but can be
present with an abnormal pH
o Expected change in pCO2 best used for primary
metabolic disturbance and expected change in
HCO3 for primary respiratory disturbance
 Diagnosis of acid Base Disorder

3. Primary Metabolic Disturbance:

o Calculate anion gap : Na – (Cl + HCO3)
o Normal = 12 +/- 2
o If gap is >20 then there is primary metabolic
acidosis regardless of pH or bicarb.
o Helps narrow differential with a anion gap or
non- anion gap metabolic acidosis
 Diagnosis of acid Base Disorder

4. Assess appropriate respiratory

compensation for metabolic disorder:
o Respiratory compensation is fast
o Winters formula:
Expected pCO2 = (1.5 * HCO3) + 8 (+/-2)
o If measured pCO2 is
< expected then co-existing resp. alkalosis
> expected then co-existing resp. acidosis
 Diagnosis of acid Base Disorder

5. Determine if other metabolic

disturbances co- exist with AG metabolic
acidosis:
o Delta gap – accounts for increase in anion gap
and shows any variation in HCO3
o If no other disorder is present then the
calculation should be 24
Corrected HCO3 = measured HCO3 + (AG - 12) o So
if corrected HCO3
>24 then metabolic alkalosis co-exists
<24 then non-anion gap metabolic acidosis co-exists
 Normal values

pH 7.35 – 7.45
PCO2 35 – 45mmHg
PO2 80 -100mmHg
K+ 3.5 – 5.0meq/l
Na+ 135 -145meq/l
Cl- 98 – 108mmol/l
HCO3- 22 – 26meq/l
Anion gap 9 - 16
Golden rules: Simple acid-base disorders
1) PCO2 and HCO3 always change in the same direction.
2) The secondary physiologic compensatory mechanisms
must be present.
3) The compensatory mechanisms never fully correct
pH.
Simple Acid-Base Disorders
Look at the pH in order to determine the primary
abnormality
Pathophysiologic principle: body does not fully
compensate even for chronic acid-base disorders
The secondary physiologic compensatory
mechanisms must be present
Example #1
pH 7.50 Acute Respiratory
Alkalosis
pCO2 29
HCO3 22 Variable Primary Normal Primary
Disorder Range, Disorder
arterial Gas

pH Acidemia 7.35-7.45 Alkalemia

pCO2 Respiratory 35 - 45 Respiratory

alkalosis acidosis

HCO3 Metabolic 22 – 26 Metabolic

acidosis Alkalosis
Respiratory alkalosis
Reduced carbon dioxide due to increased alveolar
ventilation

Buffering processes lower plasma bicarbonate

concentration (rapid but limited response, ~1-2 meq/l)

Kidney response is to reduce net acid excretion

(eliminate bicarbonate into the urine or decrease
ammonium excretion). Delayed response, 1-2 days)
Respiratory Alkalosis Compensation
Acute
Plasma [HCO3-] is lowered by 2mEq/L for every 10-mm
Hg decrease in PaCO2
Chronic
Plasma [HCO3-] is lowered by 5mEq/L for every 10-mm
Hg decrease in PaCO2
Example #2
pH 7.25 Acute Respiratory
Acidosis
pCO2 60
HCO3 26 Variable Primary Normal Primary
Disorder Range, Disorder
arterial Gas

pH Acidemia 7.35-7.45 Alkalemia

pCO2 Respiratory 35 - 45 Respiratory

alkalosis acidosis

HCO3 Metabolic 22 – 26 Metabolic

acidosis Alkalosis
Respiratory acidosis
Induced by hypercapnia (decreased alveolar ventilation)

Buffering mechanisms raise plasma bicarbonate

concentration (rapid but limited response, ~1-2 meq/l)

Kidney minimizes the change in extracellular pH by

increasing acid excretion (NH4+) generating new
bicarbonate ions (delayed response, 2-3 days).
Acute respiratory acid base disorders always have a
greater change in pH than chronic disorders
Respiratory disorders
Acute respiratory acid base disorders always have a
greater change in pH than chronic disorders
Plasma Cl changes equally and inversely with plasma
HCO3.
Plasma anion gap does not change with respiratory
disorders
Plasma sodium is not directly altered by acid base
disorders
Example #3
pH 7.34 Chronic Respiratory
Acidosis with Metabolic
pCO2 60 Compensation
HCO3 31 Variable Primary Normal Primary
Disorder Range, Disorder
arterial Gas

pH Acidemia 7.35-7.45 Alkalemia

pCO2 Respiratory 35 - 45 Respiratory

alkalosis acidosis

HCO3 Metabolic 22 – 26 Metabolic

acidosis Alkalosis
Example #4
pH 7.50 Metabolic Alkalosis

pCO2 48
HCO3 36 Variabl Primary Normal Primary
e Disorder Range, Disorder
arterial Gas

pH Acidemia 7.35-7.45 Alkalemia

pCO2 Respiratory 35 - 45 Respiratory

alkalosis acidosis

HCO3 Metabolic 22 – 26 Metabolic

acidosis Alkalosis
Causes of Metabolic Alkalosis
Processes that raise plasma bicarbonate concentration

 Vomiting (loss of H+ from GIT)

 Diuretics (loss of H+ in urine)
 Excess mineralocorticoid activity—Cushing’s syndrome,
Conn’s syndrome, exogenous steroids, licorice ingestion,
increased renin states, Bartter’s syndrome [ Excessive urinary
net acid excretion (primary hyperaldosteronism)]
 Excess alkali administration
 Refeeding alkalosis
Example #5
pH 7.20 Metabolic Acidosis with
Respiratory Compensation
pCO2 21
HCO3 8 Variabl Primary Normal Range, Primary
e Disorder arterial Gas Disorder

pH Acidemia 7.35-7.45 Alkalemia

pCO2 Respiratory 35 - 45 Respiratory

alkalosis acidosis

HCO3 Metabolic 22 – 26 Metabolic

acidosis Alkalosis
Causes of Metabolic Acidosis

Acidemia created by increase in [H+] or decrease in

[HCO3-]
Compensated for by hyperventilation to reduce PaCO2
 Non-Gap
 GI HCO3 loss: diarrhea, intestinal fistulas, ureteral diversions
 Renal HCO3 loss: RTA, aldosterone inhibitors, carbonic
anhydrase inhibitors
 Iatrogenic: normal saline
 Anion Gap
 Ketoacidosis: diabetic, alcoholic
 Renal failure
 Lactic Acidosis
 Rhabdomyolysis
 Toxins: methanol, ethylene glycol, paraldehyde, salicylates
 Dietary protein intake (Animal source)
Sodium and Chloride relationship
Law of electro neutrality:

Sodium concentration is not directly altered by acid base

disorders
Plasma Cl is altered in all acid base disorders (except
increased plasma anion gap metabolic acidosis)
Conclusion: If sodium concentration stays constant but
chloride conc changes, an acid base disorder is present
Mixed Acid-base disorders
The presence of more than one simple acid-base
disorder simultaneously:
Respiratory acidosis and metabolic acidosis (profound
acidemia)
Respiratory alkalosis and metabolic alkalosis (profound
alkalemia)
Metabolic alkalosis and respiratory acidosis
Metabolic acidosis and respiratory alkalosis
 The Rules
Look at the pH: whichever side of 7.40 the pH is on, the
process that caused it to shift to that side is the primary
abnormality
 Principle: the body doesn’t fully compensate for primary acid-base
disorders
Calculate the anion gap: Na – (Cl + HCO3): if the anion gap
is >20, there is a primary metabolic acidosis regardless of pH
or HCO3
 Principle: the body doesn’t generate a large anion gap to compensate
for a primary disorder
Calculate the excess anion gap (total anion gap minus the
normal anion gap) and add this to the measured HCO3
concentration, if >30, there is underlying metabolic alkalosis;
if <24, there is underlying non-gap metabolic acidosis
 Principle: 1 mmol of unmeasured acid titrates 1 mmol of bicarbonate
Understanding the anion gap

Each millimolar decrease in HCO3 is accompanied by a

millimolar increase in the anion gap, the sum of the new
(excess) anion gap and the remaining (measured)
HCO3 value should be equal to a normal bicarbonate
concentration
Anion Gap
 The sum of cations and anions in
AG = Na+ - (Cl- + HCO3-)
ECF is always equal , so as to
maintain the electrical neutrality.

 Normal range = 9-16mEq/l  Commonly measured electrolytes

High AG acidosis in plasma are Na+, K+,Cl-,HCO3-
I. Renal failure
II. Diabetic ketoacidosis  Unmeasured anion in the
III. Lactic acidosis plasma constitutes the anion
Normal AG acidosis gap.
IV. Diarrhoea  This is due to presence of
V. Hyperchloremic acidosis protein anions, sulphate ,
Low AG phosphate and organic acids.
Multiple myeloma
 Example #6
pH 7.50
pCO2 20 Respiratory Alkalosis and
HCO3 15 Anion Gap Metabolic
Na 140 Acidosis
Cl 103 Variable Primary Normal Primary
Disorder Range, Disorder
arterial Gas
1. Look at the pH to determine the
primary process. pH Acidemia 7.35-7.45 Alkalemia
2. Calculate the anion gap: Na – (Cl +
HCO3) pCO2 Respiratory 35 - 45 Respiratory
3. Calculate the excess anion gap (total alkalosis acidosis
anion gap minus the normal anion
gap) and add this to the measured
HCO3 concentration, if >30, there is HCO3 Metabolic 22 – 26 Metabolic
acidosis Alkalosis
underlying metabolic alkalosis; if
<24, there is underlying non-gap
metabolic acidosis
 Example #7
pH 7.40
pCO2 40 Anion Gap Metabolic
HCO3 24 Acidosis and Metabolic
Na 145 Alkalosis
Cl 100 Variable Primary Normal Primary
Disorder Range, Disorder
arterial Gas
1. Look at the pH to determine the
primary process. pH Acidemia 7.35- Alkalemia
2. Calculate the anion gap: Na – (Cl + 7.45
HCO3) pCO2 Respiratory 35 - 45 Respiratory
3. Calculate the excess anion gap (total alkalosis acidosis
anion gap minus the normal anion
gap) and add this to the measured
HCO3 concentration, if >30, there is HCO3 Metabolic 22 – 26 Metabolic
acidosis Alkalosis
underlying metabolic alkalosis; if
<24, there is underlying non-gap
metabolic acidosis
What’s the Diagnosis?

Chronic renal failure in a patient with vomiting as his

uremia worsened.
 Example #8
pH 7.50 Respiratory alkalosis,
pCO2 20 Anion Gap Metabolic
HCO3 15 Acidosis and Metabolic
Na 145 Alkalosis
Cl 100 Variable Primary Normal Primary
Disorder Range, Disorder
arterial Gas
1. Look at the pH to determine the
primary process. pH Acidemia 7.35-7.45 Alkalemia
2. Calculate the anion gap: Na – (Cl +
HCO3) pCO2 Respiratory 35 - 45 Respiratory
3. Calculate the excess anion gap (total alkalosis acidosis
anion gap minus the normal anion
gap) and add this to the measured
HCO3 concentration, if >30, there is HCO3 Metabolic 22 – 26 Metabolic
acidosis Alkalosis
underlying metabolic alkalosis; if
<24, there is underlying non-gap
metabolic acidosis
What’s the Diagnosis?
History of vomiting (metabolic alkalosis),
alcoholic ketoacidosis (metabolic acidosis),
and bacterial pneumonia (respiratory
alkalosis)
 Example #9
pH 7.10 Respiratory Acidosis,
pCO2 50 Anion gap Metabolic
HCO3 15 Acidosis, Metabolic
Na 145 Alkalosis
Cl 100 Variable Primary Normal Primary
Disorder Range, Disorder
arterial Gas
1. Look at the pH to determine the
primary process. pH Acidemia 7.35-7.45 Alkalemia
2. Calculate the anion gap: Na – (Cl +
HCO3) pCO2 Respiratory 35 - 45 Respiratory
3. Calculate the excess anion gap (total alkalosis acidosis
anion gap minus the normal anion
gap) and add this to the measured
HCO3 concentration, if >30, there is HCO3 Metabolic 22 – 26 Metabolic
acidosis Alkalosis
underlying metabolic alkalosis; if
<24, there is underlying non-gap
metabolic acidosis
What’s the Diagnosis?
Patient presented in an obtunded state (respiratory
acidosis), history of vomiting (metabolic alkalosis),
DKA (anion gap metabolic acidosis)

Or

Chronic respiratory acidosis and metabolic

compensation in whom an acute anion gap
metabolic acidosis developed
 Example #10
pH 7.15 Anion Gap and Non-Anion
pCO2 15 Gap Metabolic Acidoses
HCO3 5
Na 140
Cl 110 Variable Primary Normal Primary
Disorder Range, Disorder
arterial Gas
1. Look at the pH to determine the
primary process. pH Acidemia 7.35-7.45 Alkalemia
2. Calculate the anion gap: Na – (Cl +
HCO3) pCO2 Respiratory 35 - 45 Respiratory
3. Calculate the excess anion gap (total alkalosis acidosis
anion gap minus the normal anion
gap) and add this to the measured
HCO3 concentration, if >30, there is HCO3 Metabolic 22 – 26 Metabolic
acidosis Alkalosis
underlying metabolic alkalosis; if
<24, there is underlying non-gap
metabolic acidosis
What’s the Diagnosis?
DKA with non-gap acidosis during recovery phase of
DKA due to failure to regenerate HCO3 from keto-acids
lost in the urine
Conclusions
Acid-base disturbances are easy to analyze if
approached systematically
Determine primary abnormalities based on pH
Calculate the anion gap
Calculate the delta gap and add to the measured HCO3
Calculate an anion gap on EVERY chemistry you see
If there is an elevated anion gap, remember to get an
ABG!!
pH (7.35-7.45) Normal !! ?

suggests:
 no acid-base disturbance
 chronic respiratory alkalosis
 chronic respiratory acidosis (mild)
 mixed disturbance
What is this Acid-Base Disorder?
25 year-old male, heroin overdose
pH 7.10 PaCO2 80 HCO3- 24
What is this Acid-Base Disorder?
25 year-old male, heroin overdose
pH 7.10 PaCO2 80 HCO3- 24
Acidemic, PaCO2 is elevated, acute change
Acute respiratory acidosis ([HCO3-] unchanged)
What is this Acid-Base Disorder?
55 year-old man with COPD
pH 7.32 PaCO2 70 HCO3- 35
What is this Acid-Base Disorder?
55 year-old man with COPD
pH 7.32 PaCO2 70 HCO3- 35
Acidemic, PaCO2 is elevated  respiratory acidosis
What is this Acid-Base Disorder?
55 year-old man with COPD
pH 7.23 PaCO2 90 HCO3- 35
What is this Acid-Base Disorder?
55 year-old man with COPD
pH 7.23 PaCO2 90 HCO3- 35
Acidemic, PaCO2 is elevated  respiratory acidosis
 the bicarb has not compensated appropriately yet,
indicating an acute respiratory acidosis on a chronic
respiratory acidosis
What is the Acid-Base Disorder?
62 year-old woman with pneumonia for 1 week
pH 7.46 PaCO2 20 HCO3- 14
What is the Acid-Base Disorder?
62 year-old woman with pneumonia for 1 week
pH 7.46 PaCO2 20 HCO3- 14
Alkalemic, PaCO2 is decreased  respiratory alkalosis
What is the Acid-Base Disorder?
62 year-old woman with pneumonia for 1 week
pH 7.46 PaCO2 20 HCO3- 14
Alkalemic, PaCO2 is decreased  respiratory alkalosis
Is the bicarb what you would expect?
What is the Acid-Base Disorder?
62 year-old woman with pneumonia for 1 week
pH 7.46 PaCO2 20 HCO3- 14
Alkalemic, PaCO2 is decreased  respiratory alkalosis
Is the bicarb what you would expect?
Yes, PaCO2 decreased by 20, so would expect bicarb to
decrease by 10 in chronic respiratory alkalosis
What is the Acid-Base Disorder?
23 year-old woman with seizure for 90 minutes.
pH 7.24 PaCO2 36 HCO3- 14
What is the Acid-Base Disorder?
23 year-old woman with seizure for 90 minutes.
pH 7.24 PaCO2 36 HCO3- 14
Acidemic, PaCO2 is decreased  metabolic acidosis
What is the anion gap?
 Na+ 140 Cl- 100 HCO3- 14
Anion Gap = 26
Why is this elevated?
What is the Acid-Base Disorder?
29 year-old pregnant woman who is vomiting.
pH 7.58 PaCO2 48 HCO3- 40
What is the Acid-Base Disorder?
29 year-old pregnant woman who is vomiting.
pH 7.58 PaCO2 48 HCO3- 40
Alkalemic, PaCO2 is increased  metabolic alkalosis
Scenario 5
22 year-old man, upset that he broke up with his
girlfriend, was found confused, next to a bottle of pills.
What is the acid-base disorder? What is the ingestion?
pH 7.53 PaCO2 15 HCO3- 12 Na+ 140 Cl- 108 CO2 13
Scenario 5
pH 7.53 PaCO2 15 HCO3- 12 Na+ 140 Cl- 108 CO2 13
What is the pH?
Scenario 5
pH 7.53 PaCO2 15 HCO3- 12 Na+ 140 Cl- 108 CO2 13
What is the pH?
Alkalosis
What is the PaCO2?
Scenario 5
pH 7.53 PaCO2 15 HCO3- 12 Na+ 140 Cl- 108 CO2 13
What is the pH?
Alkalosis
What is the PaCO2?
Low  respiratory alkalosis
What is the anion gap?
Scenario 5
pH 7.53 PaCO2 15 HCO3- 12 Na+ 140 Cl- 108 CO2 13
What is the pH?
Alkalosis
What is the PaCO2?
Low  respiratory alkalosis
What is the anion gap?
19  Anion gap metabolic acidosis
Scenario 5
Metabolic acidosis with respiratory alkalosis
What is the ingestion?
Scenario 5
Metabolic acidosis with respiratory alkalosis
What is the ingestion?
Aspirin