Costanzo | Physiology | Chapter 7 | Acid Base Physiology | Study Guide
Chapter 7: Acid-Base Physiology Notes
I. pH of Body Fluids
Hydrogen Ion Concentration ([H+]): Normal arterial [H+] is extremely low, approximately 40 nEq/L.
pH Scale: Because [H+] is such a small number, it is expressed as pH=−log10[H+]. The normal pH of arterial blood is 7.4.
Acidemia vs. Alkalemia: A pH<7.37 is called acidemia (increased [H+]); a pH>7.42 is called alkalemia (decreased [H+]) [689f].
II. Acid Production in the Body
Volatile Acid: Carbon dioxide (CO2) is produced by aerobic metabolism. While not an acid itself, it reacts with water to form the weak acid H2CO3. CO2 is "volatile" because it is excreted by the lungs.
Fixed Acid (Nonvolatile Acid): Metabolism of proteins and phospholipids produces approximately 50 mmol/day of fixed acids (e.g., sulfuric and phosphoric acids). These cannot be expired and must be buffered in body fluids and eventually excreted by the kidneys.
III. Buffering
Principles: A buffer consists of a weak acid and its conjugate base. It resists changes in pH by converting strong acids/bases into weak ones.
Henderson-Hasselbalch Equation: Used to calculate pH: pH=pK+log[HA][A−].
Extracellular Buffers:
HCO3−/CO2 System: The most important extracellular buffer (pK=6.1). It is highly effective because CO2 is volatile and regulated by the lungs, while HCO3− is regulated by the kidneys.
Inorganic Phosphate (HPO4−2/H2PO4−): pK=6.8. It is more important as a urinary buffer.
Intracellular Buffers:
Organic Phosphates (ATP, ADP, 2,3-DPG).
Proteins: The most significant is hemoglobin in red blood cells. Deoxyhemoglobin is a more effective buffer than oxyhemoglobin.
IV. Renal Mechanisms in Acid-Base Balance
The kidneys maintain balance through two primary processes:
Reabsorption of Filtered HCO3−: Almost 99.9% is reabsorbed, primarily in the proximal tubule via Na+−H+ exchange. This process does not excrete H+ but conserves existing HCO3−.
Excretion of Fixed H+:
Titratable Acid: H+ is secreted and combines with filtered phosphate buffer (HPO4−2). This results in the reabsorption of "new" HCO3− [718, 719f].
NH4+ Excretion: NH3 is synthesized from glutamine in the proximal tubule. H+ is secreted and "trapped" as NH4+. This is the most important mechanism for excreting large H+ loads.
V. Acid-Base Disorders
Metabolic Acidosis: ↓[HCO3−]. Caused by fixed acid gain (e.g., ketoacidosis) or HCO3− loss (e.g., diarrhea). Respiratory compensation is hyperventilation (↓PCO2).
Metabolic Alkalosis: ↑[HCO3−]. Caused by H+ loss (e.g., vomiting) or HCO3− gain. Respiratory compensation is hypoventilation (↑PCO2).
Respiratory Acidosis: ↑PCO2. Caused by hypoventilation (e.g., COPD). Renal compensation is increased HCO3− reabsorption and new HCO3− synthesis.
Respiratory Alkalosis: ↓PCO2. Caused by hyperventilation (e.g., high altitude). Renal compensation is decreased HCO3− reabsorption.
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Chapter 7 Study Guide
I. Glossary of Key Terms
Anion Gap: The difference between measured cations (Na+) and measured anions (Cl−+HCO3−). Normal range: 8–16 mEq/L.
Bohr Effect: Increased H+ concentration shifting the O2-hemoglobin curve to the right to facilitate O2 unloading.
Fixed Acid: A nonvolatile acid (e.g., sulfuric acid) that must be excreted by the kidneys.
Isohydric Line: A line on an acid-base map representing all combinations of PCO2 and [HCO3−] that yield the same pH.
Metabolic Disorder: A primary disturbance in the [HCO3−] concentration.
Respiratory Disorder: A primary disturbance in the PCO2 concentration.
Titratable Acid: H+ excreted in urine bound to a buffer, primarily phosphate.
Volatile Acid: CO2, which can be converted to H2CO3 and expired by the lungs.
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II. 50 Question-and-Answer Quiz
What is the normal arterial blood pH? 7.4.
What is the normal [H+] in arterial blood? 40 nEq/L.
Which acid is produced at 13,000 to 20,000 mmol/day? CO2 (volatile acid).
What is the primary source of fixed acids? Catabolism of proteins and phospholipids.
What does a pH of 7.0 represent in terms of acid-base status? Acidemia [689f].
What is the pK of the HCO3−/CO2 buffer system? 6.1.
What is the solubility coefficient of CO2 in blood? 0.03 mmol/L/mm Hg.
Where is the majority of filtered HCO3− reabsorbed? Proximal tubule.
Which enzyme catalyzes CO2+H2O⇌H2CO3? Carbonic anhydrase.
What is the primary intracellular buffer? Proteins (especially hemoglobin) and organic phosphates.
Which form of hemoglobin is a better buffer for H+? Deoxyhemoglobin (pK=7.9).
What happens to the O2-Hb curve during acidemia? It shifts to the right (Bohr effect).
How much fixed acid is produced daily? 50 mEq/day.
What is the maximum H+ concentration gradient the kidney can maintain? Minimum urine pH is 4.4.
Which urinary buffer is responsible for titratable acid? Phosphate (HPO4−2).
What is the pK of the phosphate buffer? 6.8.
From which amino acid is NH3 synthesized? Glutamine.
Where is NH3 primarily produced in the nephron? Proximal tubule.
What is "diffusion trapping"? NH3 diffusing into the lumen and reacting with H+ to form NH4+, which cannot diffuse back.
What is the formula for the plasma anion gap? [Na+]−([Cl−]+[HCO3−]).
Name two causes of an increased anion gap metabolic acidosis. Diabetes (ketoacids), strenuous exercise (lactic acid), or salicylate overdose.
What is the respiratory compensation for metabolic acidosis? Hyperventilation (↓PCO2).
What is the respiratory compensation for metabolic alkalosis? Hypoventilation (↑PCO2).
Which disorder is caused by an primary increase in PCO2? Respiratory acidosis.
Which disorder is caused by a primary decrease in PCO2? Respiratory alkalosis.
What defines a "simple" acid-base disorder? Only one primary disturbance and its expected compensation.
What is the "rule of thumb" for PCO2 change in metabolic acidosis? 1 mEq/L↓[HCO3−]=1.3 mm Hg↓PCO2 [736t].
In which disorder does the pH increase and [HCO3−] increase? Metabolic alkalosis [736t].
What causes hyperchloremic metabolic acidosis? Diarrhea or renal tubular acidosis (normal anion gap).
What are the unmeasured anions in the anion gap? Plasma proteins, phosphate, citrate, and sulfate.
What is the primary disturbance in chronic obstructive pulmonary disease? Respiratory acidosis (↑PCO2).
Does vomiting cause metabolic acidosis or alkalosis? Metabolic alkalosis.
What effect does Na+ depletion (ECF volume contraction) have on HCO3− reabsorption? It increases it (contraction alkalosis).
Which hormone stimulates NH3 synthesis during chronic acidosis? No specific hormone mentioned; acidosis itself up-regulates the enzymes.
What is the pH when [A−]=[HA]? pH=pK.
What is the effective buffering range of a buffer? pK±1.0 pH units.
How does the body handle the 13,000 mmol of CO2 produced daily? Exhalation by the lungs.
Which transporter moves H+ into the lumen in the proximal tubule? Na+−H+ exchanger.
Which cell type in the late distal tubule secretes H+? α-intercalated cells [719f].
What is the effect of aldosterone on H+ secretion? It stimulates it [729t].
Is the anion gap increased in diarrhea? No, it is a normal anion gap acidosis.
What is the most significant intracellular buffer? Hemoglobin.
What happens to the anion gap in starvation? It increases due to ketoacid production.
What does a PCO2 of 60 mm Hg and HCO3− of 36 mEq/L represent? A pH of 7.4 (compensation for chronic respiratory acidosis).
What is the effect of hyperventilation on arterial pH? It increases pH (alkalemia).
What is the compensatory response to respiratory alkalosis? Decreased renal HCO3− reabsorption.
Can a patient have a normal pH but an acid-base disorder? Yes, if the disturbance is fully compensated.
Which buffer is most important in the urine? Phosphate.
What is the byproduct of glutamine metabolism in the kidney? NH4+ and "new" HCO3−.
What is the Henderson-Hasselbalch equation used for? Calculating the pH of a buffered solution.
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III. Short Answer Questions
Explain why the HCO3−/CO2 buffer is so effective despite its pK (6.1) being far from blood pH (7.4).
Answer: Its effectiveness comes from the fact that both components are regulated independently: CO2 by the lungs (ventilation) and HCO3− by the kidneys (reabsorption/synthesis). This allows the body to rapidly adjust the ratio to maintain pH even if the absolute concentrations change.
Describe the difference between "reabsorbed HCO3−" and "new HCO3−."
Answer: Reabsorbed HCO3− is the recovery of filtered HCO3− in the proximal tubule, which prevents loss but does not add new buffer to the blood. "New" HCO3− is synthesized by the kidneys during H+ excretion as titratable acid or NH4+, serving to replenish HCO3− consumed in buffering fixed acids.
What is the significance of the anion gap in diagnosing metabolic acidosis?
Answer: It helps distinguish between causes. An increased anion gap indicates the gain of fixed acids (like ketoacids or lactate), where HCO3− is replaced by unmeasured organic anions. A normal anion gap (hyperchloremic) indicates the loss of HCO3− (as in diarrhea), where HCO3− is replaced by Cl−.
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IV. Essay Questions
Describe the renal mechanisms for H+ excretion and HCO3− synthesis.
Answer: Discuss the secretion of H+ into the lumen. In the proximal tubule, H+ combines with filtered HCO3− for reabsorption. For excretion, H+ combines with phosphate buffers to form titratable acid (H2PO4−). Simultaneously, the kidney synthesizes NH3 from glutamine; NH3 diffuses into the lumen, combines with H+, and is trapped as NH4+ for excretion. Both processes (titratable acid and NH4+) result in the addition of "new" HCO3− to the blood.
Compare the primary disturbances and compensatory responses for the four simple acid-base disorders.
Answer: Define Metabolic Acidosis (↓[HCO3−], ↓PCO2), Metabolic Alkalosis (↑[HCO3−], ↑PCO2), Respiratory Acidosis (↑PCO2, ↑[HCO3−]), and Respiratory Alkalosis (↓PCO2, ↓[HCO3−]). Explain that the compensatory response is always in the same direction as the primary disturbance and involves the organ (lungs or kidneys) not responsible for the primary defect [726, 729t].
