Acid–Base Homeostasis

Objective 1.2.1 — Hydrogen ion concentration and pH; pH homeostasis via the lungs, kidneys, and blood buffers; CO₂ production, transport, and excretion; energy metabolism and the respiratory quotient (RQ); the oxyhemoglobin dissociation curve and the factors that shift it (pH, temperature, 2,3-DPG, Bohr/Haldane effects); and step-by-step interpretation of arterial blood gases (ROME).

Listen: Acid–Base Homeostasis

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Acid–Base Homeostasis

Objective 1.2.1 — Understand the chemistry of pH and [H⁺]; describe how the lungs, kidneys, and blood buffers maintain acid–base balance; explain how CO₂ is produced, transported, and excreted; relate energy metabolism (carbs, lipids, protein) to CO₂ production via the respiratory quotient (RQ); apply the factors that shift the oxyhemoglobin dissociation curve; and interpret arterial blood gases using the ROME mnemonic.

Acid–Base Homeostasis Review
Companion video review of acid–base homeostasis.

Hydrogen Ions and pH

The Hydrolysis Equation

CO₂ + H₂O ⇌ H₂CO₃ ⇌ [H⁺] + HCO₃⁻

This single reversible reaction is the backbone of acid–base homeostasis. Move it to the right and you generate hydrogen ion (acid). Move it to the left and you blow off CO₂ (less acid).

Hydrogen Ion [H⁺]

Free hydrogen ion concentration [H⁺] in the blood must be maintained within very narrow limits to maintain life. Alterations in [H⁺] may have profound, life-threatening effects on the chemistry of the body.

pH

Definition — pH is the customary way to express [H⁺]. It is the negative log of the free [H⁺].

ParameterNormal Arterial Range
pH7.35 – 7.45

Relationship Between pH and [H⁺] — INVERSE

Change in pHChange in [H⁺]
Increase in pHDecrease in [H⁺]
Decrease in pHIncrease in [H⁺]

pH descriptions:

  • "Inversely" proportional to [H⁺]
  • Negative log of the [H⁺]
  • Log of the reciprocal of the [H⁺]

Acid–Base Balance

TermBehaviorpH
AcidDonates / releases H⁺< 7.35
BaseAccepts H⁺> 7.45

pH Homeostasis

Maintenance of a constant internal environment is called homeostasis. Both acids and bases must be regulated closely to ensure stable levels and a normal pH. Blood pH is accomplished through the interaction of three systems:

SystemRole
LungsPrecisely maintain levels of acids/bases (rapid — minutes)
KidneysPrecisely maintain levels of acids/bases (slow — hours to days)
Blood BuffersProtective role — prevent large changes in pH when abnormal conditions expose blood to acid–base abnormalities

The Lungs and CO₂

Arterial PCO₂ at any given moment depends on:

  1. The quantity of CO₂ entering the blood from the tissues
  2. The quantity of CO₂ leaving the blood via the lungs
FactorDetermines
Metabolic rateThe quantity of CO₂ produced that enters the blood
Lung function (ventilation)The quantity of CO₂ eliminated from the blood (alveolar ventilation / gas exchange)

CO₂ Production Depends on Metabolism

CO₂ production depends on both the quantity and the nature of metabolism. The nature of metabolism depends on the type of foodstuff being burned.

Carbohydrate metabolism produces MORE CO₂ than fat metabolism.


Review of General Chemistry

Metabolism

Metabolism — the sum of all chemical processes that occur in the body. Metabolism helps with:

  • Growth
  • Energy production
  • Elimination of waste
  • Distribution of nutrients in the blood after digestion

The Mitochondria

Inside each cell is a special organelle, the mitochondria, the cell's "powerhouse", where the Krebs cycle generates energy from nutrients.

Cellular respiration is the process by which cells convert the energy of carbohydrates, proteins, and lipids into ATP.

The relationship between nutrition and respiratory status is reciprocal throughout the human life cycle. A fully functioning pulmonary system supplies the O₂ needed for cellular metabolism of the three macronutrients: carbohydrates (CHO), proteins, and lipids.


Three Sources of Energy

Energy metabolism — the process of generating energy (ATP) from nutrients.

#SourceRoleStorage
1CarbohydrateShort-term energy — body's preferred energy sourceStored in liver and muscle as glycogen or as fat
2Lipid / FatLong-term energy (e.g., brisk walking) — more energy per gram → more efficient storage. When carb metabolism is deficient, more fat is used → weight lossAdipose tissue
3ProteinGrowth and repair

CO₂ Production by Macronutrient

Carbs, lipids/fats, and proteins all produce CO₂ when broken down — just at different rates.

MacronutrientO₂ Consumed : CO₂ ProducedRatio
Carbohydrate1 mole O₂ : 1 mole CO₂1 : 1.0
Lipid / Fat1 mole O₂ : 0.7 mole CO₂1 : 0.7
Protein1 mole O₂ : 0.8 mole CO₂1 : 0.8

Respiratory Quotient (RQ)

RQ — the ratio of the patient's CO₂ production (V̇CO₂) to O₂ consumption (V̇O₂):

RQ = V̇CO₂ / V̇O₂

RQ ValueInterpretation
RQ > 1.0Suggests excessive carbohydrate or calorie provision → ↑ CO₂ production → may cause difficulty weaning from mechanical ventilation
RQ < 0.7Suggests underfeeding and use of ketones as a fuel source

Pulmonary Disorders Affected by Nutrition

  • Asthma
  • Cystic fibrosis
  • Chronic obstructive pulmonary disease (COPD)
  • Emphysema
  • Acute respiratory distress syndrome (ARDS)

Nutritional requirements and status of patients with pulmonary disease are established major factors that influence acute and long-term outcomes.


CO₂ Elimination & Excretion

In a normal respiratory system, increased CO₂ production is balanced by a parallel rise in alveolar ventilation and CO₂ excretion.

Most clinical changes in PaCO₂ are a result of changes in alveolar ventilation.

Change in Alveolar VentilationEffect on PaCO₂
Increase in alveolar ventilationDecrease in PaCO₂
Decrease in alveolar ventilationIncrease in PaCO₂

When Ventilation Can't Keep Up

Sometimes increases in CO₂ production cannot be offset by increased ventilation. This may occur when:

  • CO₂ production is high — burns, total parenteral nutrition (TPN), sepsis
  • The ventilatory system is compromised

CO₂ Transport in the Blood

CO₂ is carried in the blood in four basic forms:

  1. Dissolved CO₂
  2. Carbonic acid (H₂CO₃)
  3. Bicarbonate (HCO₃⁻)
  4. Carbamino compounds

Normal arterial PCO₂ = 40 mmHg

Carbonic Acid

The concentration of carbonic acid [H₂CO₃] in the blood varies directly with the quantity of dissolved CO₂ — the two are linked through the hydrolysis reaction.

Bicarbonate

Carbonic acid is in equilibrium with both dissolved CO₂ and bicarbonate. Some CO₂ entering the blood ultimately forms HCO₃⁻ (a relatively small amount in this direct conversion), but…

HCO₃⁻ is the major mechanism of CO₂ transport — accounting for approximately 80% of CO₂ transport from tissues to lungs.


Blood Buffers

Blood buffers serve a primarily protective role, preventing large changes in pH when abnormal conditions expose the blood to acid–base abnormalities.

What Buffers Do

  • Allow relatively large H⁺ changes to take place with relatively little change in free [H⁺]
  • Lessen the change in [H⁺]
  • Prevent extreme changes in free [H⁺]
  • Accept or donate H⁺, depending on whether there is acid or base excess
  • Convert strong acids and bases into weak acids and bases
  • Maintain a narrow range of free [H⁺] required to sustain life

Two Major Buffer Systems

Major SystemWhere
HemoglobinInside the RBC
Kidneys

Red Blood Cells (RBCs / Erythrocytes)

  • Hemoglobin in RBCs is the major buffer
  • Reversible binding of [H⁺] occurs with every RBC

Other Buffers

  • Bicarbonate — HCO₃⁻
  • Phosphate — HPO₄
  • Ammonia — NH₃⁻

Gas Exchange and Transport Review

Oxygen Transport

Form% of Total
Bound to hemoglobin98.5%
Dissolved in plasma1.5%

Haldane Effect governs how much O₂ Hb is willing to carry.

Carbon Dioxide Transport

Form% of Total
Bound to hemoglobin (carbamino compounds)23%
Dissolved in plasma7%
Bound with water as HCO₃⁻70%

Bohr Effect governs how Hb's affinity for O₂ changes when CO₂/H⁺ change.


Factors Affecting O₂ Loading and Unloading on Hemoglobin

Beyond the shape of the HbO₂ curve, three big factors shift it:

  1. Blood pH
  2. Body temperature
  3. Erythrocyte concentration of 2,3-DPG

pH and the HbO₂ Curve

pHCurve ShiftsHb Affinity for O₂
Low pH (acidic)RightDecreases (Hb gives up O₂ more easily — unloading)
High pH (alkalotic)LeftIncreases (Hb holds onto O₂ — loading)

Body Temperature and the HbO₂ Curve

Body TempCurve ShiftsHb Affinity for O₂
Decrease in body tempLeftIncreases
Increase in body tempRightDecreases

2,3-DPG and the HbO₂ Curve

2,3-DPG (2,3-diphosphoglycerate) is an organic phosphate found in abundance in RBCs. It forms a loose chemical bond with the globin chains of deoxygenated Hb.

2,3-DPGCurve ShiftsHb Affinity for O₂
HIGH 2,3-DPGRightDecreases (promotes O₂ unloading)
LOW 2,3-DPGLeftIncreases

Bohr & Haldane Effects (Recap)

EffectWhat It Describes
Bohr EffectHow CO₂ / H⁺ / temperature affect Hb's affinity for O₂
Haldane EffectHow O₂ binding affects Hb's ability to carry CO₂

Interpreting Arterial Blood Gases (ABGs)

Normal Values

ValueNormal Range
pH7.35 – 7.45
PaCO₂35 – 45 mmHg
HCO₃⁻22 – 26 mEq/L

Acid / Base Definitions

TermDefinition
AcidosisAbnormal physiologic condition (the patient) where a strong acid is gained or base is lost — acidotic = ↓ pH
AlkalosisAbnormal physiologic condition (the patient) where a strong base is gained or acid is lost — alkalotic = ↑ pH
AcidemiaAbnormal state of the blood, pH is below normal
AlkalemiaAbnormal state of the blood, pH is above normal

ROME Mnemonic

ROME helps you tell whether an abnormality is respiratory or metabolic based on the direction of the change.

Respiratory — Opposite (PaCO₂ moves the opposite direction from pH) Metabolic — Equal (HCO₃⁻ moves the same / equal direction as pH)

Respiratory (CO₂) — INVERSE Effect on pH

PaCO₂pHDisturbance
↑ CO₂↓ pHRespiratory ACIDOSIS
↓ CO₂↑ pHRespiratory ALKALOSIS

Metabolic (HCO₃⁻) — DIRECT Effect on pH

HCO₃⁻pHDisturbance
↑ HCO₃⁻↑ pHMetabolic ALKALOSIS
↓ HCO₃⁻↓ pHMetabolic ACIDOSIS

Blood Gas Components Summary

ComponentTypeRelationship to pH
pHBoth — metabolic and respiratory
PaCO₂RespiratoryInverse — ↑ PaCO₂ → ↓ pH
HCO₃⁻MetabolicLinear / Direct — ↑ HCO₃⁻ → ↑ pH
BE / BD (Base Excess / Base Deficit)MetabolicLinear / Direct — ↑ → ↑ pH

How to Interpret an ABG — 7 Steps

  1. Categorize the pH
    • Acidotic — less than 7.4
    • Alkalotic — greater than 7.4
  2. Evaluate CO₂ — is it normal? 35 – 45 mmHg
  3. Evaluate HCO₃⁻ — is it normal? 22 – 26 mEq/L
  4. What is causing the pH to be abnormal? — apply ROME
  5. Is there compensation? — none, partial, or fully compensated. Is the other organ helping out?
  6. Assess for hypoxemia — abnormally low level of O₂ in the blood
  7. Assess for hypoxia — deficient amount of O₂ reaching the tissues (global or local)

The Four Primary Acid–Base Disorders (Acute / Uncompensated)

1. Respiratory Acidosis

↑ PaCO₂ → ↓ pH

Cause: HYPOVENTILATION — decreased alveolar ventilation relative to the rate of CO₂ production.

Common etiologies:

  • COPD
  • Neuromuscular disorder
  • Drug / sedation overdose
  • ROSC (return of spontaneous circulation)

2. Respiratory Alkalosis

↓ PaCO₂ → ↑ pH

Cause: HYPERVENTILATION — increased alveolar ventilation relative to CO₂ production.

Common etiologies:

  • Acute asthma
  • Pulmonary embolism
  • Fever
  • Pregnancy
  • Hypoxia

3. Metabolic Acidosis

↓ HCO₃⁻ → ↓ pH

Cause: Loss of base or gain of acid.

Common etiologies:

  • Ketoacidosis
  • Lactic acidosis
  • Renal failure
  • Diarrhea
  • Salicylate (Aspirin) poisoning

4. Metabolic Alkalosis

↑ HCO₃⁻ → ↑ pH

Cause: Gain of base or loss of acid.

Common etiologies:

  • Fluid lost from the GI tract
  • Severe vomiting
  • N-G tube complications
  • Diuretics
  • Severe potassium depletion
  • Excess administration of HCO₃⁻

Quick Reference

Hydrolysis Equation

CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻

Normal ABG Values

ValueNormal
pH7.35 – 7.45
PaCO₂35 – 45 mmHg
HCO₃⁻22 – 26 mEq/L

ROME at a Glance

Respiratory = Opposite · Metabolic = Equal

Up/DownpH ↑pH ↓
PaCO₂ ↑Respiratory Acidosis
PaCO₂ ↓Respiratory Alkalosis
HCO₃⁻ ↑Metabolic Alkalosis
HCO₃⁻ ↓Metabolic Acidosis

RQ Pearls

  • RQ = V̇CO₂ / V̇O₂
  • RQ > 1.0 → overfeeding / excess CHO → ↑ CO₂ → trouble weaning
  • RQ < 0.7 → underfeeding → ketones as fuel
  • Carbs 1.0 · Lipids 0.7 · Protein 0.8

Curve Shifts — Memory Aid

Right shift = Release O₂ to tissues (low affinity). Left shift = Load / Lock onto O₂ (high affinity).

Right Shift (↓ Affinity)Left Shift (↑ Affinity)
↑ Temp · ↓ pH (acidic) · ↑ 2,3-DPG↓ Temp · ↑ pH (alkalotic) · ↓ 2,3-DPG

CO₂ Transport Breakdown

80% as HCO₃⁻ · 23% on Hb (carbamino) · 7% dissolved in plasma. (Hb-bound vs. dissolved figures focus on tissue-to-lung carriage; HCO₃⁻ is the dominant mechanism overall.)

"Patient" vs. "Blood" Vocabulary

  • Acidosis / Alkalosis = the patient's physiologic condition
  • Acidemia / Alkalemia = the blood's pH state

The Four Disorders — Cause in One Word

DisorderOne-Word Cause
Respiratory acidosisHypoventilation
Respiratory alkalosisHyperventilation
Metabolic acidosisAcid gain / base loss (e.g., DKA, diarrhea)
Metabolic alkalosisBase gain / acid loss (e.g., vomiting, NG suction)