Acid base disorders & Blood gas analysis

Acid (H+) Definition: 

substance that can yield a hydrogen ion when dissolved in H2O

Base Definition:

(bicarbonate) or OH- (hydroxide ion) - substance that can ACCEPT H+

pH Definition: 

inversely proportional to [H+]

Critical pH

7.35 - 7.45 in the human body

pH below 7.35 is an acidemia, and a pH above 7.45 is an alkalemia

Neutral pH Definition: 

7, on a scale of 1 to 14

Normal arterial blood pH Definition: 

@ 37°C is 7.40 ± 0.05

Normal venous blood pH Definition: 

@ 37°C is 7.37 ± 0.05

Metabolically Produced Acids

• Volatile acid = CO2 (~20 moles produced each day by normal metabolism)

• Nonvolatile acids: non CO2  (~100 mmoles/day by normal metabolism)

Nonvolatile acids

acids derived from sources other than CO2

• uric acid, phosphoric acid, sulfuric acid, acetoacetic acid, etc.

• cannot be removed through lungs and must be excreted through the kidney

Types of Buffer Systems

• Bicarbonate/carbonic acid buffer system: H(+) + HCO3 ⇌ H2CO3 ⇌ CO2 + H2O

• Protein buffer: Most circulating proteins carry a net negative charge capable of binding H+

  • Albumin: accounts for about 95% of the buffering capacity of proteins

• Phosphate buffer: HPO4^2- & H2PO4 - in plasma and RBC pH balance (2,3 DPG)

Acid-Bicarbonate Buffer System

When H⁺ increases in the body, it combines with HCO₃⁻ (bicarbonate) to form H₂CO₃ (carbonic acid) → breaks down into CO₂ and H₂O.

• system neutralizes excess acidity through reactions that involve sodium bicarbonate (NaHCO₃) → allowing bicarbonate to buffer excess H⁺

  • prevents significant pH changes

Acidosis vs Alkalosis

• Acidosis: CO₂ → More H₂CO₃ forms → More H⁺ is released → pH drops (acidosis)

• Alkalosis: CO₂ → Less H₂CO₃ forms → Less H⁺ is available → pH rises (alkalosis)

Controlling Blood pH - Buffers

• pH imbalance due to changes in HCO₃⁻ → metabolic and primarily regulated by the kidneys

• pH imbalance due to changes in CO₂ → respiratory and primarily regulated by the lungs

Causes of Increased Acidity in the body: Respiratory

• Chronic Obstructive Pulmonary Disease (COPD), severe asthma, pneumonia

• Respiratory depression (opioids, sedatives)

Causes of Increased Acidity in the body: Metabolic

• Metabolic causes:

  • Diabetic ketoacidosis (DKO)

  • Lactic acidosis

  • Kidney failure

  • severe diarrhea

  • Alcoholic ketoacidosis

  • Certain medications (aspirin overdose, metformin)

  • Starvation

  • Poisoning (ethylene glycol, methanol)

Causes of increased base/alkalinity in the body

• Excessive vomiting (loss of stomach acid)

• Overuse of antacids or baking soda

• Certain medications (diuretics)

• Hyperventilation (breathing too rapidly)

• Severe dehydration

• Milk-alkali syndrome

Predominance levels of CO2 content in blood

1. HCO₃⁻ (Bicarbonate) ~ 90-95%

2. Dissolved CO₂ (Physically dissolved gas) ~ 5%

3. H₂CO₃ (Carbonic Acid) <1

• Measuring bicarbonate levels provides the most accurate total CO₂ content in the blood.

  • H2CO3 is unstable

Respiratory vs Metabolic Control

Lungs regulate CO2 levels through ventilation (Fast), while kidneys manage bicarbonate and hydrogen ion balance (slow).

Lungs (Respiratory Control)

Control CO2 (acid) levels through ventilation - fast response

• Hyperventilation: increases CO2 elimination and raises pH

  • Ex: In response to diabetic ketoacidosis

• Hypoventilation: decreases CO2 elimination and lowers pH

Hyperventilation

A physiological condition where increased breathing rate leads to excessive elimination of CO2, resulting in a rise in blood pH. It often occurs in response to metabolic disturbances like diabetic ketoacidosis.

Hypoventilation

A condition characterized by decreased breathing rate or depth, leading to elevated CO2 levels and a lowered blood pH.

Kidneys (Metabolic Control)

Control HCO3- (base) levels through reabsorption/excretion, slow response

• Reabsorb HCO3 in the proximal convoluted tubule

• Excrete H+ ions in exchange with Na+ (regulated by aldosterone)

• Produce NH3 to buffer excess H+ and form NH4+ for excretion

• Ex: Metabolic Alkalosis = excessive vomiting = H+ loss = HCO3- secretion by kidney

ROME

Respiratory Opposite, Metabolic Equal.

• In respiratory disorders, pH and PCO2 move in opposite directions (acidosis: pH↓, PCO2↑; alkalosis: pH↑, PCO2↓).

• In metabolic disorders, pH and HCO3- move together (acidosis: pH↓, HCO3-↓; alkalosis: pH↑, HCO3-↑).

Henderson-Hasselbalch Equation

• pH = pK + log [HCO3-]/[H2CO3]

  • H2CO3 is measured as dissolved CO2 (PCO2)

• Normal ratio of base to acid is approximately 20:1

• CO2 content = HCO3- + H2CO3 (where H2CO3 = PCO2 × 0.03)

References Ranges for Adult Arterial Blood Gas (ABG)

Parameter, Normal Range

• pH: 7.35 - 7.45

• pCO2: 35 - 45 mm Hg

• pO2: 80-100 mm Hg

• HCO3-: 22 - 26 mmol/L

• TCO2: 23-27 mmol/L

• O2 saturation: 94 - 100%

• BE: -2 to +2

Kidney Function

• Absorb:

  • Bicarbonate for pH balance

• Excrete:

  • H+ ions (in acidosis)

  • Bicarbonate (in alkalosis)

  • Phosphate (acid-base regulation)

  • Potassium for electrolyte balance

• Generate:

  • Bicarbonate through buffering mechanisms

Clinical Causes of Acid-Base Disorders

Primary Acid-Base Disorders

• Respiratory acidosis: ↑ PCO2, ↓ pH (hypoventilation)

• Respiratory alkalosis: ↓ PCO2, ↑ pH (hyperventilation)

• Metabolic acidosis: ↓ HCO3-, ↓ pH (increased acid production or bicarbonate loss)

• Metabolic alkalosis: ↑ HCO3-, ↑ pH (increased bicarbonate or loss of H+)

Respiratory acidosis:

If pH is low and bicarbonate (HCO₃⁻) is high, the elevated bicarbonate is a compensatory response, not the primary cause of the acidosis

Respiratory alkalosis:

CO₂ deficit (↓ pCO₂, ↑ pH), where the excessive loss of CO₂ leads to an increase in pH

Metabolic acidosis:

If pH is low AND pCO2 is low, CO2 (and therefore the lungs) is not the culprit – it is trying to compensate

Metabolic alkalosis:

If both pH and pCO₂ are high, the elevated pCO₂ is a compensatory response, not the primary cause of the disturbance.

Imbalance Summary

The respiratory system compensates slowly for disturbances in the metabolic system and vice versa. Respiratory acidosis from CO2 retention prompts bicarbonate increase, while respiratory alkalosis from CO2 loss causes bicarbonate decrease. In metabolic acidosis, respiration increases to expel CO2, whereas in metabolic alkalosis, respiration slows to retain CO2.

Compensation Mechanism

• If respiratory system is disturbed, metabolic system compensates (slowly)

• If metabolic system is disturbed, respiratory system compensates (quickly)

Amount of Compensation:

• No compensation: primary disorder with no compensatory response

• Partial compensation: primary disorder with incomplete compensatory response

• Complete compensation: primary disorder with full compensatory response and *pH returned to normal*

Diagnostic Criteria for Acid-Base Disorders

• If pH is low and PCO2 is low: metabolic acidosis with respiratory compensation

• If pH is low and HCO3 is high: respiratory acidosis with metabolic compensation

• If pH and PCO2 are both high: metabolic alkalosis with respiratory compensation

• If pH is high and PCO2 is low: respiratory alkalosis with metabolic compensation

Red Blood Cells (Compensation Mechanisms)

• Chloride shift: bicarbonate diffuses out of RBCs during buffering; chloride diffuses in to

  maintain electrical neutrality

• Isohydric shift: oxygen binding/release from hemoglobin affects H+ release with minimal pH change

Chloride Shift

Bicarbonate diffuses RBC to plasma during buffering, leading chloride to enter RBC to maintain electrical neutrality

Upon CO2 expulsion from the lungs, chloride moves back to plasma and buffers combine with the free H+.

Isohydric Shift

Isohydric = same H+

• The process by which blood manages to carry 20 moles of CO2 from peripheral tissues to lungs

  • Normal arterial blood pH @ 37°C is 7.40 → .05

  • Normal venous blood pH @ 37°C is 7.37 → .05

Both lungs and kidneys play a major role in maintaining blood pH.

Isohydride Shift: Lungs

Oxygen from the lungs forms oxyhemoglobin in blood. H+ from deoxyhemoglobin in venous blood combines with HCO3- to form carbonic acid, which dissociates into CO2 and H2O. CO2 is exhaled, buffering H+, resulting in minimal pH change.

Isohydride Shift: Kidneys

Kidneys reabsorb bicarbonate (HCO3-) in the proximal convoluted tubule. Aldosterone promotes Na+ reabsorption, exchanging it for excess K+ or H+. Renal cells, rich in carbonic anhydrase, provide a continuous bicarbonate supply.

H+ ions secreted with Na+ may react with phosphate to form phosphoric acid. Glutamate dehydrogenase converts glutamic acid to NH3, which combines with H+ to form NH4+ for excretion. The process restores sodium and bicarbonate in plasma while excreting H+, ammonia, and non-volatile acids.

Base Excess (BE)

• Calculated perimeter which describes excess or deficit of base or bicarbonate

  • + BE = Increased base

  • - BE = decreased base

  • Normal BE 0 ± 2

• Decreased base excess is an indicator of metabolic acidosis

• Increased base excess is an indicator of metabolic alkalosis

Blood Gas Analysis (ABG)

A test that measures the levels of oxygen, carbon dioxide, and pH in the blood to assess respiratory and metabolic function.

ABG Sample Requirements

• Arterial puncture required if PO2 is to be measured (venous blood almost always has PO2 = 40 mmHg)

• No tourniquet and no fist-clenching during collection

• Use glass syringe and do not pull on plunger; do not use vacutainer

• Only heparin (liquid or dry) is acceptable; other anticoagulants alter pH

• Protect from air (anaerobic) to prevent equilibration with atmospheric CO2 and O2

• Immediately expel any small bubbles

• Keep sample submerged in ice/water slush to retard WBC metabolism

• pH decreases ~0.08 pH/hr @ 37°C but 1/10th that much @ 0°C

• Results are stable for 1-2 hours @ 0°C

• Volume of blood for most commercial electrodes is

Reference Ranges: Acid and Base

• pH: 7.35-7.45

• PCO2: 35-45 mmHg

• HCO3-: 22-26 mEq/L

• Base Excess (BE): 0 ± 2 mEq/L

• PO2: 80-100 mmHg (arterial)

Base Excess (BE)

• Calculated parameter describing excess or deficit of base or bicarbonate

• +BE = Increased base (metabolic alkalosis

• -BE = Decreased base (metabolic acidosis

• Normal BE = 0 ± 2 mEq/L

Clinical Assessment: Acid-Base

• Identify primary acid-base disorder

• Assess degree of compensation

• Evaluate underlying cause

• Monitor treatment effectiveness