Acid-Base Physiology

Question 1

Hyperventilation

Answer 1

increased breathing beyond what is required, given the metabolic production of carbon dioxide, to maintain a normal PaCO₂

Question 2

Normal range of PaCO₂

Answer 2

36-44 mm Hg

Question 3

Hypoventilation

Answer 3

Decreased breathing below that which is required for a given level of carbon dioxide production to maintain a normal PaCO2

Question 4

Hyperpnea

Answer 4

Increased ventilation with a normal PaCO₂ (for example, during mild to moderate exercise), i.e., the increase in ventilation is commensurate with the increase in carbon dioxide production.

Question 5

Tachypnea

Answer 5

Rapid breathing, i.e., a respiratory rate that is above normal. Although total ventilation tends to be elevated in patients who are tachypneic, alveolar ventilation may be normal or greater/lower than normal depending on the tidal volume and the amount of dead space being ventilated

Question 6

Carbon dioxide elimination is dependent upon ___ ventilation

Answer 6

Carbon dioxide elimination is dependent upon alveolar ventilation

Not necessarily total or minute ventilation

Question 7

Total ventilation [V_E]

Answer 7

V_E = V_A + V_D

a = alveolar

d = dead space

Question 8

Tractus solitarius

Answer 8

Group of neurons in the medulla whose firing increases with inspiration.

Question 9

Nucleus retroambigualis

Answer 9

Group of neurons in the medulla whose firing increases with expiration.

Question 10

Two ‘phases’ of exhalation

Answer 10

1. expiratory neurons fire to “brake” the inpiration
2. inspiratory activity is completely absent

Question 11

Electrical activity in inspiratory motor neurons during unstressed breath cycle

Answer 11

Question 12

Hering-Breuer Reflex

Answer 12

An inspiratory-inhibitory reflex stimulated by pulmonary stretch receptors in the lung during inspiration. Activity is maintained with a sustained stretch

aka slowly adapting stretch receptors

Question 13

Irritant receptors

Answer 13

Stimulated by mechanical or chemical irritation in the airways. These receptors may be partly responsible for the hyperventilation seen with acute asthma

aka rapidly adapting stretch receptors

Question 14

Pulmonary vascular receptors

Answer 14

These receptors are part of a group of non-myelinated fibers called C-fibers

Stimulation of receptors in pulmonary capillaries or the interstitium of the lung (juxtapulmonary-capillary or “J” receptors) lead to increased ventilation. These receptors may be responsible for the hyperpnea associated with pulmonary embolism and congestive heart failure as well as interstitial lung disease

Question 15

Chest wall receptors

Answer 15

Muscle spindles as well as receptors in joints and tendons may help adjust ventilation under conditions of mechanical loading, e.g., patients with airway obstruction. They may also play a role in the hyperpnea of exercise.

Question 16

Peripheral chemoreceptors

Answer 16

located in the aortic arch and at the bifurcation of the internal and external carotid arteries (receptors in the aortic arch have relatively minor, if any, role in control of breathing in humans); provide input about the PaO₂, PaCO₂, and pH.

Question 17

Central chemoreceptors

Answer 17

Located below the ventral surface of the medulla; detect changes in the PCO₂/pH of brainstem interstitial fluid

Question 18

Ventilatory responses to hypoxemia and hypercapnia are measured in ___ experiments.

Answer 18

Ventilatory responses to hypoxemia and hypercapnia are measured in rebreathing experiments.

Question 19

Hypoxic Ventilatory Response

Answer 19

Hypoxemia results in minimal stimulation of ventilation until the PaO₂ decreased to less than 60 mmHg. Stimulation comes from peripheral chemoreceptors, which appear to respond to PaO2 rather than the overall content of arterial blood.

Question 20

Ventilatory response to hypoxemia

Answer 20

Question 21

Hypercapnic Ventilatory Response

Answer 21

There is a linear relationship between alveolar ventilation and PaCO₂ levels, over a physiologic range.

An increase in PaCO₂ results in a much more pronounced increase in ventilation as compared to hypoxemia. Hypercapnia stimulates both peripheral and central chemoreceptors, resulting in an increased drive to breathe.

Question 22

Hydrogen Ion chemoreceptors

Answer 22

Hydrogen ions cross the blood brain barrier too slowly to have an impact initially on the central chemoreceptors. They do stimulate the peripheral chemoreceptors resulting in an increase in ventilation.

Carbon dioxide diffuses out of CSF as the PaCO₂ drops in the systemic circulation with increased ventilation. This lowers CSF carbon dioxide and reduces stimulation of central chemoreceptors. Over time (days), the CSF bicarbonate concentration normalizes.

Question 23

3 Phases of Ventillation Increase during Exercise

Answer 23

1. Neurological Phase - immediate phase
2. Metabolic Phase - slowly increasing ventilation during mid-phase of exercise; associated with increasing oxygen consumption
3. Compensatory Phase - more pronounced increase in ventilation after anaerobic threshold has been exceeded and metabolic acidosis ensues (the increase in ventilation helps to mitigate the acidosis); more intense exercise.

Question 24

Neurological Phase of exercise response

Answer 24

Occurs almost instantaneously, far too quickly to be explained by changes in metabolism or blood gases. Felt to be due to “neural mechanisms”- possibly connections from motor cortex to respiratory centers, from skeletal muscle to respiratory centers - or a conditioned reflex or learned response.

Question 25

Metabolic Phase of exercise response

Answer 25

With exercise up to approximately **40-60% of maximal** exercise capacity, **ventilation increases linearly with oxygen consumption** a**nd carbon dioxide production**, although the mechanism by which this occurs is not clear. There is no known receptor that monitors oxygen consumption or carbon dioxide production directly, and PaO₂ and PaCO₂ remain in the normal range, which eliminates stimulation of the chemoreceptors as the likely explanation.

Question 26

Compensatory Phase of exercise response

Answer 26

**Above 40-60%** of maximal exercise capacity, anaerobic metabolism occurs with resulting **accumulation of lactic acid** (**anaerobic threshold**). This results in further **increases in ventilation out of proportion to oxygen consumption**. **_The ventilatory system now must also operate to compensate for the developing metabolic acidosis_**_._

Question 27

Classic mistake in chronic hypercapnia

Answer 27

These patients are dependent on their “hypoxic drive to breathe” (because they are chronically hypercapnic, the CSF has adapted and has a relatively normal pH; thus, the chronic hypercapnia is not causing ongoing stimulation of the ventilatory centers) and, if they are given supplemental oxygen, they will “stop breathing.” **The above is false.** What is really observed: **The drive to breathe in these patients is very high** (probably as a result of stimulation of irritant receptors in the lung as well as acute hypoxemia and hypercapnia, and behavioral factors, e.g., shortness of breath). **While the drive to breathe is reduced slightly by the administration of oxygen, the subsequent rise in PaCO₂ is due only in part to the suppression of hypoxic drive.** **Haldane effect and ventilation/perfusion matching also occur.**

Question 28

Haldane effect

Answer 28

Shift in the carbon dioxide-hemoglobin curve to the right with addition of oxygen; i.e., **for the same carbon dioxide content, the PaCO₂ is higher because oxygen displaces CO₂ from the hemoglobin**

Question 29

Changes in ventilation/perfusion matching in hypercapnic patients or COPD patients

Answer 29

reversal of hypoxic pulmonary vasoconstriction in poorly ventilated regions of lung

Question 30

volatile vs fixed acids

Answer 30

**Volatile acids** may be released from the body via respiration **Fixed acids** have too low of a vapor pressure for this, and so must be eliminated via the kidneys

Question 31

Fixed acids in humans

Answer 31

* Phosphates * Sulfates

Question 32

\_\_\_ do the lion’s share of the work when it comes to eliminating acid from the body

Answer 32

**The lungs** do the lion’s share of the work when it comes to eliminating acid from the body 10,000 - 15,000 mEq carbonic acid eliminated by the lungs per day 50-100 mEq of sulfiric and phosphoric acid eliminated by the kidneys each day

Question 33

pH of arterial blood

Answer 33

7.40 (range 7.36-7.44)

Question 34

The body’s initial response to an acute change in pH

Answer 34

Buffers!

Question 35

The body’s long-term response to a chronic change in pH

Answer 35

compensatory processes

Question 36

Hyperventilation and hypoventilation effects on blood pH

Answer 36

Hyperventilation eliminates more CO₂ in the blood, shifting the bicarbonate equilibrium and **increasing pH (alkalosis)** Hypoventilation builds up carbonic acid in the blood, shifting the bicarbonate equilibrium and **reducing pH (acidosis).**

Question 37

Protein buffers

Answer 37

Hemoglobin: acts as a major buffer in the blood for respiratory acid (carbonic acid). CO₂ diffuses into the red blood cell where, in the presence of **carbonic anhydrase**, it forms carbonic acid, which dissociates to H⁺ and HCO₃ ^- . The proton binds to the negatively charged hemoglobin molecule, and the bicarbonate is moved outside the cell. Thus, the **initial buffering of acid** resulting from the accumulation of carbon dioxide is done by proteins and leads to a **rise in the serum bicarbonate**

Question 38

Henderson-Hasselbalch

Answer 38

Question 39

Respiratory Acidosis

Answer 39

**Decreases in alveolar ventilation** result in increase in alveolar and arterial PCO₂, which reacts with water to form carbonic acid and **reduce blood pH**. The exact arterial pH depends on the buffers in the blood and the ability of the kidneys to compensate over 48-72 hours from the onset of the primary disturbance

Question 40

Respiratory Alkalosis

Answer 40

**Alveolar ventilation in excess** of what is needed to eliminate body’s production of CO2 → leads to a decrease in PaCO2 and a **rise in pH**

Question 41

Metabolic Acidosis

Answer 41

Caused by ingestion, infusion, or production of fixed acids, reduced filtration of metabolic acids by the kidney, decreased renal secretion of hydrogen ion, movement of hydrogen ion from the intracellular to the extracellular fluid, or loss of bicarbonate

Question 42

Metabolic Alkalosis

Answer 42

Caused by excessive loss of fixed acids from the body or ingestion, infusion, or excessive renal absorption of bases such as bicarbonate

Question 43

Table of the primary acid/base disorders

Answer 43

Question 44

Respiratory Compensation

Answer 44

The body has the ability to quickly adjust ventilation to compensate for changes in hydrogen ion concentration

Question 45

Metabolic Compensation

Answer 45

Kidneys instrumental in this process. If respiratory acidosis, the kidneys can excrete excess acid (which secondarily results in increased serum bicarbonate)

Question 46

Remember, bicarbonate is . . .

Answer 46

Remember, bicarbonate is **not an effective buffer for respiratory acidosis**

Question 47

In many cases of acidosis/alkalosis, except in some cases of repsiratory alkalosis, the body . . .

Answer 47

In many cases of acidosis/alkalosis, except in some cases of repsiratory alkalosis, the body **does not fully compensate back to a normal pH for any acute acid-base disturbance.**

Question 48

Table of compensatory mechanisms for various primary pH disturbances

Answer 48

Question 49

Because of the delay in the response of the renal system to primary acid-base abnormalities of the respiratory system, one can categorize respiratory system acid-base disorders as . . .

Answer 49

Because of the delay in the response of the renal system to primary acid-base abnormalities of the respiratory system, one can categorize respiratory system acid-base disorders as **acute or chronic.** In an **acute respiratory system disturbance**, the pH changes by **0.08 units for every change of 10 mm Hg in the PaCO₂**; for a **chronic respiratory disorder**, the pH changes by **0.03 units for every 10 mm Hg change in the PaCO₂.**

Question 50

When analyzing an acid-base problem, you should ask yourself. . .

Answer 50

1. Is the pH abnormal? In what direction? 2. Is the change in PaCO₂ in the direction expected for a primary respiratory disturbance? 3. If a primary respiratory disturbance is present, is it **acute (0.08 pH units / 10 mm Hg PaCO₂)** or **chronic (0.03 pH units / 10 mm Hg PaCO₂)**? 4. If a primary metabolic disturbance is present, is there an appropriate respiratory system response?

Question 51

Stimulation of flow receptors in the airways has ___ effect on ventilation

Answer 51

Stimulation of flow receptors in the airways has **an inhibitory** effect on ventilation

Question 52

Inflation of the lung has ___ on the controller. Deflation of the lung has ___ on the controller.

Answer 52

**Inflation** of the lung, which stimulates slowly adapting stretch receptors, has an **inhibitory effect on the controller**. **Deflation** of the lung has a **stimulatory effect on the controller.**

Question 53

The peripheral chemoreceptors . . .

Answer 53

The peripheral chemoreceptors are located in the **carotid bodies** and are stimulated by **low PaO2, high PaCO2, and low arterial pH.**

Question 54

The central chemoreceptor . . .

Answer 54

The central chemoreceptor is located in the **medulla** and is activated by **high PaCO2 and low arterial pH.**

Question 55

\_\_\_ results in a counterbalancing role for the central chemoreceptor relative to the peripheral chemoreceptor when the latter is responding to acute changes in arterial pH.

Answer 55

**The differential permeability of the blood-brain barrier for carbon dioxide and hydrogen ions** results in a counterbalancing role for the central chemoreceptor relative to the peripheral chemoreceptor when the latter is responding to acute changes in arterial pH**.**

Question 56

Patients with chronic hypercapnia are ___ in order to breathe any more than healthy individuals

Answer 56

Patients with chronic hypercapnia are **_NOT_ dependent upon hypoxemia** in order to breathe any more than healthy individuals

Question 57

A respiratory acidosis is characterized by. . .

Answer 57

. . . an **increased PaCO₂**, a **decreased pH**, and ultimately an **increase in the serum bicarbonate concentration** as protons are secreted in the renal tubule

Question 58

A respiratory alkalosis is characterized by. . .

Answer 58

. . . a **decreased PaCO₂**, an **increased pH**, and a **mild decrease in the serum bicarbonate concentration.**

Question 59

A metabolic acidosis is characterized by . . .

Answer 59

. . . a **reduced bicarbonate** concentration and a **low pH**

Question 60

A metabolic alkalosis is characterized by. . .

Answer 60

. . . an **increased bicarbonate** concentration and an **elevated pH**

Question 61

 If there is evidence of an abnormal pH but the PaCO2 has moved in a direction that is opposite of what you expect for a primary respiratory disorder, . . .

Answer 61

. . . you are dealing with a primary metabolic disturbance with respiratory compensation.

Question 62

Because the lung relies on stored potential energy to exhale when at rest, if the compliance of the lung is high, then . . .

Answer 62

. . . **it will not have enough elastic recoil and stored potential energy** to push the air out again **without exerting energy from the exhalatory muscles**. This is the case in **emphysema**

Question 63

Respiratory acidosis caused by high alveolar compliance diagram

Answer 63

Question 64

Total blood CO₂

Answer 64

PCO₂ + CO2 bound to hemoglobin Remember that PCO₂ does not capture this bound CO₂!

Question 65

Even though ventilation-perfusion mismatch is very common (many COPD patients, etc), . . .

Answer 65

. . . **hypercapnia secondary to ventilation-perfusion mismatch is relatively rare**. That is because the body can usually adapt by increasing ventilation rate and effectively eliminating more CO₂ per minute from its still functioning alveoli.

Question 66

Symptoms of respiratory alkalosis

Answer 66

painful tingling in the hands and feet, numbness and sweating of the hands, and cerebral symptoms following voluntary hyperventilation.

Question 67

Normal PaO₂

Answer 67

80-100 mmHg

Question 68

You are evaluating a 75-year-old woman with chronic obstructive pulmonary disease (COPD) for a chief complain of months of shortness of breath. She describes her shortness of breath as being constantly present, but worse with exertion. As part of her evaluation, an arterial blood gas (ABG) on room air is performed, demonstrating a pH of 7.31, PaCO2 of 68mm Hg, and a PaO2 of 65mm Hg. Which of the following is most accurate interpretation of her ABG?

Answer 68

Chronic respiratory acidosis

Question 69

A patient with diffuse lung disease has led to severe ventilation/perfusion mismatch. She has chronically elevated PaCO2. Suffering from an acute bronchitis, her PaO2 falls to 50 mm Hg. She is being evaluated in the Emergency Department and is given supplemental oxygen (100%) to breathe via a mask. You predict:

Answer 69

the PaCO2 will rise, but she will not stop or severely decrease her breathing.

Question 70

Administration of supplemental oxygen to a patient with severe V/Q mismatch may lead to . . .

Answer 70

a rise in the PaCO2 due to worsening of the V/Q mismatch (more blood being sent to poorly ventilated units due to reversal of hypoxic pulmonary vasoconstriction as alveolar O2 rises with the supplemental oxygen), the Haldane effect, and a small drop in ventilation mediated by the chemoreceptors as arterial O2 rises. The patient will not stop breathing completely, however, because we do not breathe from minute to minute due to hypoxemia.

Question 71

An 'acute exacerbation' of COPD results in . . .

Answer 71

**acute increase in dead space**

Question 72

Hyperventilation vs Hyperpnea

Answer 72

Hyperventilation refers **specifically** to **abnormal** **PaCO2**, so you can have **adaptive or pathological hyperventilation.** Hyperpnea refers **specifically** to increased breathing rate with **normal PaCO2,** so you basically only ever ahve **adaptive hyperpnea.**

Question 73

Physiologic range of bicarbonate

Answer 73

~24 mEq / u