Week 2

Question 1

Question 1: Lecture 166: Control of Breathing

Learning Objective: List the names and anatomical locations of the major groups of neurons within the medullar and pons regulating breathing.

In order to investigate the role of different nuclei in the dorsal (DRG) and ventral respiratory group (VRG), an investigator developed a mouse line that expresses ArchT in the cell membrane of neurons located in specific nuclei in the DRG and VRG. ArchT is a chloride ion channel that prevents action potentials by hyperpolarizing neurons. By activating the ArchT channels with laser stimulation, the investigator can silence the activity of specific nuclei in the DRG or VRG. Based on our current understanding of the physiology of the brainstem, silencing which of the following nucleus will most likely lead to the loss of breathing rhythm due to loss of the breathing central pattern generator?

1. DRG – Nucleus Tractus Solitarii
2. Rostral VRG – Botzinger Complex
3. Intermediate VRG – Pre-Botzinger Complex
4. Caudal VRG – Nucleus Retroambigualis

Answer 1

Answer: C

1. DRG – Nucleus Tractus Solitarii; Processes visceral sensory information from CNIX and CNX and contains premotor neurons related to inspiration.
2. Rostral VRG – Botzinger Complex; Contains interneurons that project to caudal VRG. Activity of these interneurons are related to expiration.
3. Intermediate VRG – Pre-Botzinger Complex; Hypothesized to contain the breathing central pattern generator. Also contains motor and premotor neurons related to inspiration.
4. Caudal VRG – Nucleus Retroambigualis; Contains premotor neurons related to expiration.

Question 2

Learning Objectives: List common causes of hypoxemia and separate those that elevate A-a and those that do not.

Describe the subset of patients with acute hypoxemic respiratory failure

The systemic circulatory system responds to local hypoxemia by vasodilating to increase blood flow to the hypoxemic region. In contrast, the pulmonary circulatory system responds to local hypoxemia by vasoconstriction. This can cause acute mountain sickness in certain members of the population; when their pulmonary circulatory system responds to hypoxemia at high altitudes by global vasoconstriction. Why does the pulmonary circulatory system respond to hypoxemia in such a manner?

1. Increase alveolar dead space ventilation
2. Decrease alveolar dead space ventilation
3. Increase right-to-left shunt
4. Decrease right-to-left shunt

Answer 2

Answer: D

1. Alveolar dead space ventilation occurs when the local pulmonary circulation is blocked. Hypoxemia induced vasoconstriction can increase alveolar dead space ventilation, but this is not the goal of the hypoxemia induced vasoconstriction response.
2. Vasoconstriction cannot decrease alveolar dead space ventilation.
3. Vasoconstriction cannot increase right-to-left shunt.
4. Right-to-left shunt occurs when local alveolar ventilation is blocked. In order to reduce local right-to-left shunting, the local pulmonary capillary responds by vasoconstricting. This response reduces blood flow to non-ventilated alveoli while increases blood flow to ventilated alveoli.

Question 3

A patient arrives to the hospital with hypercapnia and hypoxemia. The patient accidentally inhaled a small wad of tissue, causing a right-to-left shunt in a part of his lungs. Where is the tissue paper most likely located?

1. Upper left lung
2. Upper right lung
3. Lower left lung
4. Lower right lung

Answer 3

Learning Objectives: Explain causes of hypercapnia and hypocapnia

List common causes of hypoxemia and separate those that elevate A-a and those that do not

Answer: D

1. The left main bronchus is positioned more perpendicular to the trachea than the right main bronchus. It is less likely for a foreign object to fall into the left lung.
2. The right main bronchus is positioned more parallel to the trachea than the left main bronchus. It is more likely for a foreign object to fall into the right lung. However, there is less perfusion of the upper lungs as compared to the lower lungs due to gravity. Thus, blockage of the upper lung is less likely to cause hypercapnia and hypoxemia.
3. The left main bronchus is positioned more perpendicular to the trachea than the right main bronchus. It is less likely for a foreign object to fall into the left lung.
4. The right main bronchus is positioned more parallel to the trachea than the left main bronchus. It is more likely for a foreign object to fall into the right lung. Additionally, there is increased perfusion of the lower lungs as compared to the upper lungs due to gravity. Thus, blockage of the lower lung is most likely to cause hypercapnia and hypoxemia.

Question 4

An astronaut removes his breathing apparatus on an alien planet. When he takes a breath, two gases enter his lungs, gas ZZ and gas YY. The astronaut’s space suit constantly monitors the partial pressures of gases in the astronaut’s alveoli and pulmonary blood supply. The readings from his space suit shows that gas ZZ reaches dynamic equilibrium between his alveoli and pulmonary blood supply before the blood leaves his lungs. Meanwhile gas YY does not reach dynamic equilibrium between his alveoli and pulmonary blood supply before the blood leaves his lungs. Which of the following best describe gas ZZ and YY?

1. Gas ZZ is diffusion limited, gas YY is diffusion limited
2. Gas ZZ is diffusion limited, gas YY is perfusion limited
3. Gas ZZ is perfusion limited, gas YY is diffusion limited
4. Gas ZZ is perfusion limited, gas YY is perfusion limited

Answer 4

Learning Objectives: Explain the factors determining whether alveolar-capillary gas exchange is “perfusion” or “diffusion” limited and the implications of each for gas transport

Answer: C

A gas that reaches equilibrium between the alveoli and the pulmonary blood supply before the blood finishes traversing the pulmonary capillaries cannot be diffusion limited. It is only limited by perfusion; the faster the heart pumps, the more of the gas can enter the body. This describes gas ZZ. A gas that does not reach equilibrium between the alveoli and the pulmonary blood supply before the blood finishes traversing the pulmonary capillaries is diffusion limited. In this case, even a faster heart rate will not increase the total amount of the gas that can enter the body. This describes gas YY. Only answer C matches this description.

Question 5

Which of the following best describes the Haldane effect and the CO2-Bohr effect, respectively?

1. Haldane: Increased binding of O2 to hemoglobin increases dissociation of CO2 from the blood. Bohr: Hypercapnia increases binding of O2 to hemoglobin.
2. Haldane: Increased binding of O2 to hemoglobin increases dissociation of CO2 from the blood. Bohr: Hypercapnia decreases binding of O2 to hemoglobin.
3. Haldane: Decreased binding of O2 to hemoglobin increases dissociation of CO2 from the blood. Bohr: Hypercapnia increases binding of O2 to hemoglobin.
4. Haldane: Decreased binding of O2 to hemoglobin increases dissociation of CO2 from the blood. Bohr: Hypercapnia decreases binding of O2 to hemoglobin.

Answer 5

Learning Objectives: Describe the Haldane effect

Answer: B

The Haldane effect states that increased binding of O2 to hemoglobin increases dissociation of CO2 from the blood. This guarantees that when the CO2 laden venous blood enters the lungs, which has a high O2 content in the alveoli, CO2 will be rapidly dissociated to be exchanged with the atmosphere. The CO2-Bohr effect states that hypercapnia decreases biding of O2 to hemoglobin. This ensures that when the O2 laden arterial blood enters metabolically active tissue, which has a high CO2 content due to respiratory oxidation, O2 will be rapidly dissociated to continue feeding the mitochondria. Only answer B matches these descriptions.

Question 6

In the Davenport diagram above, a patient’s blood pH and bicarb are resting at point 1. His pH and bicarb levels then move to point 2. After some time, his blood pH and bicarb finally settle at point 3. Which of the following best describes the patient’s condition?

1. Metabolic compensation to primary respiratory acidosis
2. Respiratory compensation to primary metabolic alkalosis
3. Respiratory compensation to primary metabolic acidosis
4. Metabolic compensation to primary respiratory alkalosis

Answer 6

Learning Objective: Explain the effects of the addition or subtraction of an acid or base on the bicarbonate and other buffer systems

Answer: B

Movement from point 1 to point 2 is an example of primary metabolic alkalosis. There is an increase in pH without changing the partial pressure of CO2 in the blood. This may have resulted from excessive vomiting or ingestion of a base. Subsequent movement from point 2 to point 1 is an example of respiratory compensation to the metabolic alkalosis. Breathing has decreased to increase partial pressure of CO2 in the blood in order to generate more protons to lower blood pH. Although pH has been normalized, the patient now must deal with hypercapnia. Only choice B matches this description.

Question 7

What is the sum of functional residual capacity (FRC) and inspiratory capacity (IC)?

1. Total lung capacity (TLC)
2. Vital capacity (VC)
3. Residual volume (RV)
4. Tidal volume (TV)

Answer 7

Learning objectives: Define the main lung volumes and capacities

Describe the relationship amongst minute ventilation, alveolar ventilation and dead space

Answer: A

TLC = IC+FRC

IC = TV + IRV; IRV = inspiratory reserve volume

FRC = ERV + RV; ERV = expiratory reserve volume

Question 8

Decreasing the radius of the bronchi by 10 nm will increase airway resistance by a factor of?

1. 10
2. 100
3. 1000
4. 10000

Answer 8

Learning objectives: Describe the relationship amongst minute ventilation, alveolar ventilation and dead space

Answer: D

Airway resistance is proportional to (nl)/(r^4); n = viscosity of air, l = length of airway, r = radius of airway. Thus, changing the radius of the airway has a tremendous affect on airway resistance.

Question 9

During your pulmonary critical care rotation, the attending doctor asks you to calculate the A-a gradient of a patient. The patient has an arterial O2 partial pressure of 80 mmHg, an arterial CO2 partial pressure of 40 mmHg. Assume that the atmosphere pressure is 760 mmHg, that the H2O partial pressure in the air is 47 mmHg, that the inspired air is 21% O2, and that the patient’s respiratory quotient is 0.8. What is the best estimate for the A-a gradient for this patient?

1. 100
2. 50
3. 20
4. 10

Answer 9

Learning objective: Calculate the A-a difference on room air and the ratio of PaO2 to FiO2 in an intubated patient on supplemental oxygen and describe how these calculations inform clinical practice. List common causes of hypoxemia and separate those that elevate A-a and those that do not

C

The simplified alveolar gas equation is P_AO2 = (P_ATM-P_H2O)*FiO2-P_ACO2/RQ; P_AO2 = alveolar partial pressure of O2, P_ATM = atmospheric pressure, P_H2O = partial pressure of H2O in air, FiO2 = fraction of inspired air that is O2, P_ACO2 = alveolar partial pressure of CO2 (which you can assume to be equal to arterial partial pressure of CO2), RQ = respiratory quotient. Thus P_AO2 = (760-47)*0.21-40/0.8 = 99.7 ~ 100. Thus P_AO2 – P_aO2 = 100 – 80 = 20.

Question 10

A 25 yo Caucasian male comes to the clinic complaining of dyspnea on excursion. The patient does not smoke or drink alcohol. Neither do his parents and close relatives. He recently graduated college and is working at a tech start up. His FEV1 is 60% of his forced vital capacity and he has a large total lung capacity. On physical exam, the physician notes that the patient is thin and expires through pursed lips. He also uses accessory respiratory muscles to breath, especially the strap muscles of his neck. Which of the most likely cause of the patient’s symptoms?

1. Chronic bronchitis due to second hand smoke
2. Idiopathic pulmonary fibrosis
3. Silicosis
4. Emphysema due to a1-antitrypsin deficiency

Answer 10

Learning Objective: Describe the unifying features of obstructive lung disease in contrast to restrictive lung disease

Answer: D

1. In chronic obstructive pulmonary disease, patients often have decreased FEV1/FEC ratio and an increased TLC and RV. A patient with predominant chronic bronchitis often can be described as a “blue bloater.” The patient is often overweight and cyanotic, with chronic cough and sputum production, and often in no apparent distress or use of accessory muscles.
2. Idiopathic pulmonary fibrosis is a restrictive lung disease. The patient would have increased FEV1/FEC ratio and a decreased TLC and RV.
3. Silicosis is a restrictive lung disease and is usually associated with exposure to mining, stone cutting, or glass manufacturing.
4. In chronic obstructive pulmonary disease, patients often have decreased FEV1/FEC ratio and an increased TLC and RV. A patient with predominant emphysema often can be describe as a “pink puffer.” The patient is often thin due to increased energy expenditure to breathing, uses accessory muscles to breath, leans forward to breath, exhales through pursed lips, and may be barrel chested. Our patient most closely fits a primarily emphysema disease. In addition, because of his young age and lack of exposure to second hand smoke, the patient is more likely to have a1-antitrypsin deficiency.

Question 11

A 30 yo African American woman comes to the clinic complaining about dyspnea, malaise , fever, and weight loss. She does not smoke and rarely drinks alcohol. Her FEV1 is 90% of her forced vital capacity and she has a smaller than normal total lung capacity. She also has decreased diffusing capacity for carbon monoxide. On lung biopsy, the patient is found to have nonaseating granulomas. Which of the following is the most likely cause of the patient’s symptoms?

1. Sarcoidosis
2. Emphysema
3. Chronic bronchitis
4. Idiopathic pulmonary fibrosis

Answer 11

Learning objective: Describe the classification of ILD into 1) diseases of known cause or association; 2) idiopathic interstitial pneumonias; 3) granulomatous diseases; and 4) miscellaneous interstitial diseases

• Explain the coomon pulmonary function abnormalities seen in ILDs*
• Explain the role of careful history, physical exam, radiographic studies, serologic tests and lung biopsy in the differential diagnosis of ILDs*

Answer: A

1. Sarcoidosis occurs most often in African American women and in 75% of cases occurs before the age of 40. It often involves many organs including the lungs. Involvement of the lungs results in restrictive lung disease, with an increased FEV1/FEC ratio, decreased TLC and RV, and decreased DL_CO. The disease is associated with noncaseating granulomas.
2. Emphysema results in obstructive disease with decreased FEV1/FEC and increased TLC and RV.
3. Chronic bronchitis results in obstructive disease with decreased FEV1/FEC and increased TLC and RV.
4. Idiopathic pulmonary fibrosis is another restrictive disease with PFTs that matches this patient. However, to make a diagnosis of idiopathic pulmonary fibrosis, other types of ILDs must be excluded. In addition, idiopathic pulmonary fibrosis occurs more often in men and smokers. In this case, sarcoidosis is the more likely cause of the patient’s symptoms.

Question 12

A 7 yo Caucasian boy presents to the clinic with dyspnea. He recently immigrated with his family to the US from Eastern Europe. His FEV1 is 50% of his forced vital capacity and his total lung capacity is smaller than normal. His parents says the patient “catches the cold” more often than his brothers and sisters. The patient also seems to have “really bad smelling” stools that tend to float instead of sink. A vitamin panel test shows that the patient is deficient in vitamins A, D, E, and K. Which of the following modes of inheritance did the patient most likely acquire his disease?

1. Autosomal dominant
2. Autosomal recessive
3. Sex-linked X chromosome
4. Sex-linked Y chromosome

Answer 12

Learning Objective: Describe the mode of inheritance of cystic fibrosis

• Identify three methods of making the diagnosis of cystic fibrosis*
• Describe the relationship between CFTR dysfunction and abnormal sweat gland and lung function*
• Describe the most common clinical manifestations of CFTR mutations*

B

The patient most likely has cystic fibrosis, which is commonly diagnosed in Caucasian children. Due to impaired chloride and water transport, patients with cystic fibrosis often present with obstructive type lung disease (decreased FEV1/FVC and increased TLC and RV). Chronic pulmonary infections and pancreatic insufficiency are also common. Pancreatic insufficiency can lead to steatorrhea and deficiency of fat-soluble vitamins (A, D, E, K). Cystic fibrosis is autosomal recessive.