15 The Effects of Pregnancy, Altitude, and Diving on the Respiratory System

Question 1

Pregnancy

• The respiratory system during pregnancy is affected by…
• As gestation progresses,…
• Functional residual capacity (FRC)
• Total lung capacity (TLC)
• Vital capacity
• The gravid uterus
• Tidal volume
• Respiratory rate
• Dead space/tidal volume ratio
• Minute ventilation

Answer 1

• The respiratory system during pregnancy is affected by…
  
  • Both anatomic changes and alterations in metabolism
• As gestation progresses,…
  
  • The diaphragmatic position elevates 4 cm
  • The diameter of the lower rib cage increases by as much as 5 cm
  • Gives a more barrel-chested appearance to the thorax
• Functional residual capacity (FRC)
  
  • These alterations result in a 10 - 25% reduction in FRC, predominantly due to a lower residual volume
• Total lung capacity (TLC)
  
  • Although FRC is reduced, TLC decreases only marginally
• Vital capacity
  
  • Not affected
• The gravid uterus
  
  • Does not impair diaphragmatic excursion
• Tidal volume
  
  • Increased
• Respiratory rate
  
  • Does not change
• Dead space/tidal volume ratio
  
  • Does not change
• Minute ventilation
  
  • Increased minute ventilation results in an increase in alveolar ventilation

Question 2

Pregnancy

• Most pronounced alterations in the respiratory physiology of pregnancy
• Progesterone
• Part of the increased respiratory drive results from…
• The greatly augmented minute ventilation over-compensates for…
• ABG measurements normally show…
• Alveolar air equation

Answer 2

• Most pronounced alterations in the respiratory physiology of pregnancy
  
  • Increased respiratory drive
  • Increased minute ventilation
• Progesterone
  
  • Increases throughout gestation
  • Stimulates respiratory drive directly
  • Increases the sensitivity of the respiratory center to PCO2
• Part of the increased respiratory drive results from…
  
  • Increased metabolic rate
  • Associated carbon dioxide (CO2) production (an increase of as much as 30% by the third trimester)
• The greatly augmented minute ventilation over-compensates for…
  
  • This increase in CO2 production
  • Results in a primary respiratory alkalosis with renal compensation
• ABG measurements normally show…
  
  • A pH ranging between 7.40 and 7.47
  • PCO2 ranging from 28 to 32 mmHg
• Alveolar air equation
  
  • Increased alveolar ventilation also increases PaO2

Question 3

Dyspnea during pregnancy

• Frequency of dyspnea during pregnancy
• Dyspnea during first, second, and third trimesters
• The likely mechanisms of dyspnea during normal pregnancy
• Indications of a respiratory illness rather than normal physiologic dyspnea of pregnancy

Answer 3

• Frequency of dyspnea during pregnancy
  
  • Up to 75% of pregnant women experience dyspnea at rest or with mild exertion by the 30th week of pregnancy
• Dyspnea during first, second, and third trimesters
  
  • This symptom commonly starts during the first or second trimester, before it can be explained by an increase in abdominal girth
  • The frequency of dyspnea increases during the second trimester and is reasonably stable during the third trimester
• The likely mechanisms of dyspnea during normal pregnancy
  
  • Progesterone-induced hyperventilation is at least partially responsible, since dyspnea has been shown to correlate with a low PaCO2
  • Increased mechanical load imposed by the enlarging uterus that increases the work of breathing, nasal congestion, increased pulmonary blood volume and anemia
• Indications of a respiratory illness rather than normal physiologic dyspnea of pregnancy
  
  • Abrupt onset of symptoms
  • The presence of a cough, sputum or tachypnea
  • Abnormal findings on physical exam

Question 4

Diving

• The physiologic alterations that occur during diving result primarily from…
• Boyle’s law
• For every 33 ft of seawater, ambient pressure…
• Lung volume vs. depth
• At a depth of 33 ft,…
  
  • External pressure
  • Lung volume

Answer 4

• The physiologic alterations that occur during diving result primarily from…
  
  • The increased pressure that surrounds the chest
  • Increased ambient pressure decreases the size of the chest and gas dissolved within it, as explained by Boyle’s law
• Boyle’s law
  
  • At a constant temperature, the volume of a gas varies inversely to the pressure applied to it
• For every 33 ft of seawater, ambient pressure…
  
  • Increases by one atmosphere (760 mmHg)
• Lung volume vs. depth
  
  • Since the gas in the lungs is compressible, lung volume is inversely proportional to the depth attained
• At a depth of 33 ft,…
  
  • External pressure is 1520 mmHg
  • Lung volume is cut in half

Question 5

Diving

• Gas in the compressed lung
• Partial pressures of gas in the compressed lung
• Henry’s law

Answer 5

• Gas in the compressed lung
  
  • Not changed in composition
  • i.e. air inspired from the surface will still contain 21% oxygen
• Partial pressures of gas in the compressed lung
  
  • Since the total pressure of gas in the lung increases at greater depth, the partial pressures of each gas also increase
  • Alveolar PO2 and PCO2 (and PN2) increase progressively with depth
• Henry’s law
  
  • At a constant temperature, the amount of gas dissolved in a liquid is directly proportional to the partial pressure of that gas
  • At greater depth the concentration of oxygen, carbon dioxide and nitrogen increases in the blood and tissues

Question 6

Diving

• The increased ambient pressure that accompanies diving also affects…
• The extra-thoracic pressure
• The inspiratory muscles
• Below a depth of about 1 meter, it is impossible to…

Answer 6

• The increased ambient pressure that accompanies diving also affects…
  
  • The mechanics of the respiratory system
• The extra-thoracic pressure
  
  • Opposes the normal outward elastic recoil of the chest wall
  • Leads to a reduction in FRC and TLC
• The inspiratory muscles
  
  • Must also generate more force to overcome this pressure and expand the lungs and chest wall
• Below a depth of about 1 meter, it is impossible to…
  
  • Breathe through a tube connected to the surface
  • This is because below this depth, the maximum achievable inspiratory pressure (about -100 cmH2O) cannot overcome the pressure surrounding the chest

Question 7

Breath-hold diving

• To inhibit the urge to draw a breath, breath-hold divers usually…
• During the dive, as ambient pressure increases,…
• In addition, during the breath hold,…
• The increase in PaCO2 stimulates…
• Breath-hold divers may…
• Mechanical damage to the lungs

Answer 7

• To inhibit the urge to draw a breath, breath-hold divers usually…
  
  • Hyperventilate to an alveolar PO2 of about 120 mmHg and a PCO2 of 30 mmHg
• During the dive, as ambient pressure increases,…
  
  • Alveolar PO2 and PCO2 also increase
  • This causes more O2 to diffuse from the alveolar gas into the capillary blood
• In addition, during the breath hold,…
  
  • CO2 production continues and cannot be excreted via the respiratory system, further increasing alveolar and arterial PCO2
  • Therefore, significant respiratory acidosis and acidemia may occur
• The increase in PaCO2 stimulates…
  
  • Central chemoreceptors, which increase the drive to breathe and limit breath-hold time
• Breath-hold divers may…
  
  • Lose consciousness from hypoxemia upon ascent, as the volume of the thoracic cavity increases, and the partial pressure of oxygen plummets, and drown
• Mechanical damage to the lungs
  
  • Rare in breath-hold divers since lungs cannot contain more air than would fill them to TLC at surface pressure

Question 8

Breath-hold diving

• A
• B
• C
• D
• Abbreviations
  
  • PAO2
  • PACO2
  • PaO2
  • PaCO2
  • PvO2
  • PvCO2

Answer 8

• A
  
  • Breath-hold diver hyperventilates to PAO2 of 120 and PACO2 of 25, with corresponding aterial partial pressures
• B
  
  • During descent, lung volume shrinks by 25% and alveolar and arterial PO2 and PCO2 increase
  • In this model, assume that the time of descent is so rapid, that oxygen consumption and CO2 production are insignificant between A and B
• C
  
  • During breath-hold time, oxygen consumption lowers PAO2 and carbon dioxide production increases PCO2
• D
  
  • Ascent to the surface results in further fall in PAO2 and PACO2, resulting in still lower PaO2
  • In this model, assume that the time of ascent is so rapid, that oxygen consumption and CO2 production are insignificant between C and D
• Abbreviations
  
  • PAO2: partial pressure of oxygen in the alveoli
  • PACO2: partial pressure of carbon dioxide in the alveoli
  • PaO2: partial pressure of oxygen in arterial blood
  • PaCO2: partial pressure of carbon dioxide in arterial blood
  • PvO2: partial pressure of oxygen in mixed venous blood
  • PvCO2: partial pressure of carbon dioxide in mixed venous blood

Question 9

Non-breath-hold diving

• Since breathing air from the surface is not an option, ventilation during diving…
• The most commonly used breathing support system

Answer 9

• Since breathing air from the surface is not an option, ventilation during diving…
  
  • Must be supported by a pressurized system that forces gas into the lungs
• The most commonly used breathing support system
  
  • The open circuit SCUBA (Self-Contained Underwater Breathing Apparatus)
  • This device delivers ambient pressure gas only when inhalation is initiated
  • Use of open circuit SCUBA is limited by the amount of compressed gas available in the cylinder
  • A typical cylinder can supply approximately 2100 L of gas at the surface (1 atm), but at a depth of 66 feet (3 atm), the effective volume of gas is decreased to 700 L. With a VE of 10 L/min
    
    • This gas supply would last 70 minutes, and with a VE of 20 L/min, the gas would last 35 minutes

Question 10

Complications of diving:
Barotrauma

• This term refers to…
• Barotrauma is most likely to occur…
• As ambient pressure falls, lung volume…
• Pneumothorax

Answer 10

• This term refers to…
  
  • Lung injury caused by high pressure
  • Second most common cause of death in SCUBA divers (after drowning)
• Barotrauma is most likely to occur…
  
  • When a diver who is breathing pressurized gas holds his breath during an ascent
• As ambient pressure falls, lung volume…
  
  • Increases and may lead to alveolar rupture, resulting in pneumothorax, alveolar hemorrhage, or air embolism
  • The latter occurs when pressurized alveolar gas enters the alveolar capillaries and then the arterial circulation
  • These air bubbles may then occlude flow to vital organs and tissues
• Pneumothorax
  
  • Relatively uncommon
  • Subjects with a history of spontaneous pneumothorax, bullous or cystic lung disease are at increased risk, and should be cautioned against diving

Question 11

Complications of diving:
Decompression illness

• During a dive, the PO2, PCO2, and PN2 of the extracellular and intracellular, as well as the volume of dissolved gas…
• During a rapid ascent,…
• The liberated gas bubbles can…
• Bubbles that enter the blood may…
• Bubbles in joints may cause…
• The treatment for this life-threatening condition

Answer 11

• During a dive, the PO2, PCO2, and PN2 of the extracellular and intracellular, as well as the volume of dissolved gas…
  
  • Increase
• During a rapid ascent,…
  
  • Gas pressure and solubility decrease
  • Bubbles (especially nitrogen) may form in blood vessels and tissues
• The liberated gas bubbles can…
  
  • Alter organ function by blocking vessels, rupturing or compressing tissue, or activating clotting and inflammatory cascades
• Bubbles that enter the blood may…
  
  • Impair pulmonary blood flow and cause chest pain, dyspnea, and cough (the chokes)
  • Impair cerebral blood flow causing stroke
• Bubbles in joints may cause…
  
  • Pain (the bends) or osteonecrosis
• The treatment for this life-threatening condition
  
  • Immediate re-compression, which forces the gas back into solution, followed by very slow decompression, ideally accomplished in a hyperbaric oxygen chamber
  • Administration of 100% oxygen can widen the pressure gradient for nitrogen between the trapped bubble and the circulation, thus hasten absorption of the gas

Question 12

Complications of diving:
Nitrogen narcosis

Answer 12

• Rapture of the deep
• At high ambient pressures, very high PN2 can alter CNS function and lead to euphoria, amnesia, clumsiness, and irrational behavior

Question 13

Altitude

• As we ascend,…
  
  • Total barometric pressure…
  • The fractional concentration of oxygen in the atmosphere…
• The PO2 of dry air at any altitude
• The partial pressure exerted by water vapor in the air entering the alveoli
• PIO2 equation
• PAO2 equation

Answer 13

• As we ascend,…
  
  • Total barometric pressure decreases
  • The fractional concentration of oxygen in the atmosphere does not change
• The PO2 of dry air at any altitude
  
  • ~21% of total barometric pressure
• The partial pressure exerted by water vapor in the air entering the alveoli
  
  • Fixed at 47 mmHg
• PIO2 equation
  
  • PIO2 = 0.21 X (PB – 47 mm Hg) (PB = barometric pressure)
• PAO2 equation
  
  • PAO2 = PIO2 – ( PACO2/ R) (R= respiratory exchange ratio)

Question 14

Altitude

• As altitude increases,…
• At the summit of Mt. Everest (8848 m) the barometric pressure is…
• This means that a person breathing without supplemental oxygen will have a PIO2 of about…
• If PaCO2 were 10 mmHg, this would lead to a PAO2 of…
• Assuming a normal PA-aO2 of 8 mmHg, the PaO2 would be…
• This explains why…

Answer 14

• As altitude increases,…
  
  • PAO2 and PaO2 fall
  • The drop in PaO2 stimulates chemoreceptors, and this causes…
    
    • Minute ventilation to increase
    • PaCO2 to fall
    • Arterial pH to rise (respiratory alkalosis)
• At the summit of Mt. Everest (8848 m) the barometric pressure is…
  
  • 253 mm Hg
• This means that a person breathing without supplemental oxygen will have a PIO2 of about…
  
  • 43 mmHg
• If PaCO2 were 10 mmHg, this would lead to a PAO2 of…
  
  • About 30 mmHg
• Assuming a normal PA-aO2 of 8 mmHg, the PaO2 would be…
  
  • 22 mmHg
• This explains why…
  
  • Supplemental oxygen is needed

Question 15

Altitude

• Acute exposure to hypobaric hypoxia of altitude induces many physiologic changes involving multiple organ systems that together act to…
• These physiologic changes
• Adaptation
• Healthy unacclimatized individuals may develop several medical conditions at altitude, including…

Answer 15

• Acute exposure to hypobaric hypoxia of altitude induces many physiologic changes involving multiple organ systems that together act to…
  
  • Reduce the gradient between PIO2 and tissue PO2
  • Optimize delivery and utilization of oxygen at the cellular level
• These physiologic changes
  
  • Known as acclimatization
  • Regulated by the transcription factor hypoxia-inducible factor-1-alpha (HIF-1- α)
  • Begins within minutes of ascent
  • Requires several weeks to complete
• Adaptation
  
  • The physiologic changes in response to hypobaric hypoxia over generations
  • Observed in some populations living permanently at high altitude
• Healthy unacclimatized individuals may develop several medical conditions at altitude, including…
  
  • Acute mountain sickness (AMS)
  • High altitude cerebral edema (HACE)
  • Periodic breathing of altitude
  • High altitude pulmonary edema (HAPE)

Question 16

Acute mountain sickness (AMS) and high altitude cerebral edema (HACE)

• Result from…
• Lead to…
• The “tight fit” hypothesis

Answer 16

• Result from…
  
  • Hypoxia-induced cerebral vasodilation
• Lead to…
  
  • Cerebral hyperperfusion and edema
• The “tight fit” hypothesis
  
  • Individuals with less space for cerebrospinal fluid are at higher risk for symptoms with mild edema

Question 17

Acute mountain sickness (AMS)

• Experienced when…
• Altitude at which symptoms occur
• Major symptoms
• Risk factors

Answer 17

• Experienced when…
  
  • An unacclimatized person ascends to a moderate altitude
• Altitude at which symptoms occur
  
  • There is significant intra-individual variability
  • The most susceptible individuals may be affected as low as 8000 feet
  • Nearly half of lowlanders will develop AMS at 14,000 ft
• Major symptoms
  
  • Headache, dizziness, dyspnea at rest, weakness, nausea, and sleeplessness
• Risk factors
  
  • Residence at less than 3000 feet
  • Age < 50
  • Vigorous physical exertion during or after ascent
  • Rapid ascent and obesity
  • Substances that interfere with sleep (such as alcohol, sedative-hypnotic medications or primary sleep disorders) or respiratory function
  • Subjects who have had altitude-induced illness are at high risk for recurrence

Question 18

Acute mountain sickness (AMS)

• Can be prevented by…
• What may accelerate acclimatization
• Treatment

Answer 18

• Can be prevented by…
  
  • Slow ascent (no more than 1000 ft/day once you reach 8000 – 10,000 feet)
• What may accelerate acclimatization
  
  • Daytrips to higher elevation with return to lower elevation at night (“climb high, sleep low”)
  • Adequate hydration may also be helpful
• Treatment
  
  • Descent
  • Dexamethasone (a corticosteroid which reduces cerebral edema)
  • Acetazolamide (a carbonic anhydrase inhibitor)
    
    • Probably exerts its beneficial effects by inhibiting sodium and bicarbonate reabsorption in the proximal tubule, thereby promoting bicarbonate and sodium excretion
    • Bicarbonate wasting improves serum alkalemia, and sodium excretion reduces brain edema
  • These medications are also effective prophylaxis in subjects with prior AMS who are unable to ascend slowly
  • Acetazolamide, but not dexamethasone, accelerates acclimatization in addition to improving AMS symptoms

Question 19

High altitude cerebral edema (HACE)

• HACE
• Symptoms
• Therapy

Answer 19

• HACE
  
  • Least common form of high altitude illness
  • Life threatening if not rapidly recognized and treated
• Symptoms
  
  • May begin several days after ascent
  • Include headache, loss of coordination, confusion and coma
  • Autopsy studies show cerebral edema, microhemorrhages and brain herniation
• Therapy
  
  • No good studies of therapy exist
  • Oxygen and dexamethasone are commonly prescribed
  • Descent as soon as possible is the most important intervention

Question 20

Periodic breathing of altitude

Answer 20

• Both alkalosis and hypoxia contribute to high-altitude periodic breathing during sleep, a form of Cheyne-Stokes respiration
• Overstimulation of the carotid chemoreceptors leads to hyperpnea (hyperventilatory period) followed by compensatory apnea which may awaken the individual from non-REM sleep

Question 21

High altitude pulmonary edema (HAPE)

• Non-cardiogenic pulmonary edema is frequently associated with…
• HAPE
• HAPE vs. AMS and HACE
• Risk factors for HAPE

Answer 21

• Non-cardiogenic pulmonary edema is frequently associated with…
  
  • Rapid ascents above 12,000 feet.
• HAPE
  
  • Can be fatal
  • Responsible for the majority of deaths due to high altitude disease
• HAPE vs. AMS and HACE
  
  • Approximately half of subjects with HAPE also have symptoms of AMS
  • The hypoxia associated with HAPE worsens AMS and may predispose to progression to HACE
• Risk factors for HAPE
  
  • Male gender
  • Cold ambient temperatures
  • Vigorous exertion
  • Conditions associated with pre-existing pulmonary blood flow abnormalities
    
    • Primary pulmonary hypertension
    • Left to right intracardiac shunts

Question 22

High altitude pulmonary edema (HAPE)

• HAPE is characterized by…
• Together, these lead to…
• Symptoms
• Physical findings
• Most susceptible

Answer 22

• HAPE is characterized by…
  
  • Markedly elevated pulmonary artery pressures
  • Exaggerated and uneven pulmonary vasoconstriction
  • Inadequate production of endothelial nitric oxide
  • Over production of endothelin
• Together, these lead to…
  
  • Regional overperfusion
  • Breakdown of the alveolar capillary barrier
  • Patchy pulmonary edema
• Symptoms
  
  • Typically appear two to four days after arrival at a new altitude
  • Include…
    
    • Dyspnea out of proportion to exertion or that doesn’t improve with rest
    • Cough
    • Production of frothy or rusty sputum
• Physical findings
  
  • Tachypnea, crackles, jugular venous distention, and in severe cases cyanosis
• Most susceptible
  
  • Children and people with prior episodes

Question 23

High altitude pulmonary edema (HAPE)

• Genetic factors that influence susceptibility to HAPE
• Prophylactic therapy

Answer 23

• Genetic factors that influence susceptibility to HAPE
  
  • Differences in the structure or function of sodium channels expressed on type II pneumocytes, which transport fluid out of the alveolar space
  • Impaired sodium channel function makes it more difficult for sodium (and thus water) to traverse the alveolar epithelium and be absorbed into the blood
  • Polymorphisms in the endothelial nitric oxide synthase gene, the angiotensin converting enzyme gene and certain human leukocyte antigens
• Prophylactic therapy
  
  • Beta-agonists, which increase sodium channel expression in lung epithelium

Question 24

High altitude pulmonary edema (HAPE)

• Best preventive measure
• Current therapy of HAPE
• Medications

Answer 24

• Best preventive measure
  
  • Slow ascent (as with AMS)
• Current therapy of HAPE
  
  • Descent
  • Portable hyperbaric oxygen chamber (Gamow bag)
  • Supplemental oxygen, if available
• Medications
  
  • Nifedipine (a calcium channel blocker), tadalfil or sildenafil (phosphodiesterase-5 inhibitors) and beta-agonists are all used empirically, since they would be predicted to decrease PA pressures in HAPE-susceptible individuals, though few clinical trials of treatment exist
  • These same medications have proven helpful for prophylaxis of HAPE, although studies are generally small