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.
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⁺].
| Parameter | Normal Arterial Range |
|---|---|
| pH | 7.35 – 7.45 |
Relationship Between pH and [H⁺] — INVERSE
| Change in pH | Change in [H⁺] |
|---|---|
| Increase in pH | Decrease in [H⁺] |
| Decrease in pH | Increase in [H⁺] |
pH descriptions:
- "Inversely" proportional to [H⁺]
- Negative log of the [H⁺]
- Log of the reciprocal of the [H⁺]
Acid–Base Balance
| Term | Behavior | pH |
|---|---|---|
| Acid | Donates / releases H⁺ | < 7.35 |
| Base | Accepts 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:
| System | Role |
|---|---|
| Lungs | Precisely maintain levels of acids/bases (rapid — minutes) |
| Kidneys | Precisely maintain levels of acids/bases (slow — hours to days) |
| Blood Buffers | Protective 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:
- The quantity of CO₂ entering the blood from the tissues
- The quantity of CO₂ leaving the blood via the lungs
| Factor | Determines |
|---|---|
| Metabolic rate | The 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.
| # | Source | Role | Storage |
|---|---|---|---|
| 1 | Carbohydrate | Short-term energy — body's preferred energy source | Stored in liver and muscle as glycogen or as fat |
| 2 | Lipid / Fat | Long-term energy (e.g., brisk walking) — more energy per gram → more efficient storage. When carb metabolism is deficient, more fat is used → weight loss | Adipose tissue |
| 3 | Protein | Growth and repair | — |
CO₂ Production by Macronutrient
Carbs, lipids/fats, and proteins all produce CO₂ when broken down — just at different rates.
| Macronutrient | O₂ Consumed : CO₂ Produced | Ratio |
|---|---|---|
| Carbohydrate | 1 mole O₂ : 1 mole CO₂ | 1 : 1.0 |
| Lipid / Fat | 1 mole O₂ : 0.7 mole CO₂ | 1 : 0.7 |
| Protein | 1 mole O₂ : 0.8 mole CO₂ | 1 : 0.8 |
Respiratory Quotient (RQ)
RQ — the ratio of the patient's CO₂ production (V̇CO₂) to O₂ consumption (V̇O₂):
RQ = V̇CO₂ / V̇O₂
| RQ Value | Interpretation |
|---|---|
| RQ > 1.0 | Suggests excessive carbohydrate or calorie provision → ↑ CO₂ production → may cause difficulty weaning from mechanical ventilation |
| RQ < 0.7 | Suggests 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 Ventilation | Effect on PaCO₂ |
|---|---|
| Increase in alveolar ventilation | Decrease in PaCO₂ |
| Decrease in alveolar ventilation | Increase 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:
- Dissolved CO₂
- Carbonic acid (H₂CO₃)
- Bicarbonate (HCO₃⁻)
- 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 System | Where |
|---|---|
| Hemoglobin | Inside 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 hemoglobin | 98.5% |
| Dissolved in plasma | 1.5% |
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 plasma | 7% |
| 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:
- Blood pH
- Body temperature
- Erythrocyte concentration of 2,3-DPG
pH and the HbO₂ Curve
| pH | Curve Shifts | Hb Affinity for O₂ |
|---|---|---|
| Low pH (acidic) | Right | Decreases (Hb gives up O₂ more easily — unloading) |
| High pH (alkalotic) | Left | Increases (Hb holds onto O₂ — loading) |
Body Temperature and the HbO₂ Curve
| Body Temp | Curve Shifts | Hb Affinity for O₂ |
|---|---|---|
| Decrease in body temp | Left | Increases |
| Increase in body temp | Right | Decreases |
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-DPG | Curve Shifts | Hb Affinity for O₂ |
|---|---|---|
| HIGH 2,3-DPG | Right | Decreases (promotes O₂ unloading) |
| LOW 2,3-DPG | Left | Increases |
Bohr & Haldane Effects (Recap)
| Effect | What It Describes |
|---|---|
| Bohr Effect | How CO₂ / H⁺ / temperature affect Hb's affinity for O₂ |
| Haldane Effect | How O₂ binding affects Hb's ability to carry CO₂ |
Interpreting Arterial Blood Gases (ABGs)
Normal Values
| Value | Normal Range |
|---|---|
| pH | 7.35 – 7.45 |
| PaCO₂ | 35 – 45 mmHg |
| HCO₃⁻ | 22 – 26 mEq/L |
Acid / Base Definitions
| Term | Definition |
|---|---|
| Acidosis | Abnormal physiologic condition (the patient) where a strong acid is gained or base is lost — acidotic = ↓ pH |
| Alkalosis | Abnormal physiologic condition (the patient) where a strong base is gained or acid is lost — alkalotic = ↑ pH |
| Acidemia | Abnormal state of the blood, pH is below normal |
| Alkalemia | Abnormal 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
| PaCO₂ | pH | Disturbance |
|---|---|---|
| ↑ CO₂ | ↓ pH | Respiratory ACIDOSIS |
| ↓ CO₂ | ↑ pH | Respiratory ALKALOSIS |
Metabolic (HCO₃⁻) — DIRECT Effect on pH
| HCO₃⁻ | pH | Disturbance |
|---|---|---|
| ↑ HCO₃⁻ | ↑ pH | Metabolic ALKALOSIS |
| ↓ HCO₃⁻ | ↓ pH | Metabolic ACIDOSIS |
Blood Gas Components Summary
| Component | Type | Relationship to pH |
|---|---|---|
| pH | Both — metabolic and respiratory | — |
| PaCO₂ | Respiratory | Inverse — ↑ PaCO₂ → ↓ pH |
| HCO₃⁻ | Metabolic | Linear / Direct — ↑ HCO₃⁻ → ↑ pH |
| BE / BD (Base Excess / Base Deficit) | Metabolic | Linear / Direct — ↑ → ↑ pH |
How to Interpret an ABG — 7 Steps
- Categorize the pH
- Acidotic — less than 7.4
- Alkalotic — greater than 7.4
- Evaluate CO₂ — is it normal? 35 – 45 mmHg
- Evaluate HCO₃⁻ — is it normal? 22 – 26 mEq/L
- What is causing the pH to be abnormal? — apply ROME
- Is there compensation? — none, partial, or fully compensated. Is the other organ helping out?
- Assess for hypoxemia — abnormally low level of O₂ in the blood
- 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
| Value | Normal |
|---|---|
| pH | 7.35 – 7.45 |
| PaCO₂ | 35 – 45 mmHg |
| HCO₃⁻ | 22 – 26 mEq/L |
ROME at a Glance
Respiratory = Opposite · Metabolic = Equal
| Up/Down | pH ↑ | 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
| Disorder | One-Word Cause |
|---|---|
| Respiratory acidosis | Hypoventilation |
| Respiratory alkalosis | Hyperventilation |
| Metabolic acidosis | Acid gain / base loss (e.g., DKA, diarrhea) |
| Metabolic alkalosis | Base gain / acid loss (e.g., vomiting, NG suction) |