Respiratory Physiology Flashcards
Explain the role of peripheral chemoreceptors in respiration. What are they are more responsive to?
o More responsive to changes in the oxygen content of blood but also respond to changes in pH and carbon dioxide.
o Carotid bodies: bilaterally @ bifurcation of common carotids; pass from Hering’s nerves to the glossopharyngeal nerves and onto the dorsal respiratory group
o Aortic bodies: @ aortic arch; pass from the vagus nerve to the dorsal respiratory group
o These bodies are constantly exposed to only arterial blood
Based on the oxygen-hemoglobin dissociation curve, what is the PO2 when 50% of Hb is saturated?
PO2 at 27 mmHg when Hb 50% saturated (P50 = 27mmHg)
The oxygen dissociation curve plots the % saturation against the partial pressure of oxygen, and its contribution to the total oxygen content. This is an S shaped curve due to the alterations in hemoglobin’s affinity for oxygen in response to other physiologic factors such as pH and temperature.
A reduction of PO2 below 60 mm Hg causes a rapid decrease in amount of O2 bound to hemoglobin. However, diffusion of oxygen from hemoglobin to tissue cells is enhanced by this process.
The P50 represents the partial pressure at which hemoglobin is 50 percent saturated with oxygen. P50 provides a means of quantifying the hemoglobin’s affinity with oxygen and reflects the dissociation curves.
Right shift – hemoglobin has decreased affinity, increased P50 – takes more oxygen to reach 50% (higher partial pressure to get 50% saturated)
Left shift – increased affinity, decreased P50 – less oxygen to reach 50% (less partial pressure to get 50% saturated)
Describe the cough reflex.
Bronchi and trachea are very sensitive to light touch (larynx and carina especially sensitive) Afferent signals pass from the respiratory passageways to the medulla by way of the vagus nerve. The initiates an influx of air and subsequent closure of the epiglottis and vocal folds to trap the air in the lungs. The abdominal muscles contract and forcefully expel the air.
Describe the sneeze reflex.
Irritants in the nose send afferent signals to the medulla by way of CN V
Describe what occurs with control of normal breathing (nervous control).
Normal quiet breathing is controlled by repetitive inspiratory signals from dorsal respiratory group transmitted to diaphragm; expiration is passive elastic recoil of lungs and thorax.
Dorsal respiratory group come from the IX and X CN.
Describe when oxygen therapy will be effective in hypoxemia.
- 100% effective with decreased atmospheric oxygen
- Pretty effective (5x O2 delivery) with hypoventilation hypoxia
- Pretty effective with a decreased alveolar membrane diffusion because the increased PaO2 facilitates diffusion at a higher partial pressure
- Minimally effective in hypoxia caused by anemia, abnormal hemoglobin transport of oxygen, circulatory deficiency, or physiologic shunt
• Normal amounts of oxygen are already available to the alveoli • Small amount of increased O2 transport in the dissolved state may make a difference
5, Not effective in hypoxia caused by inadequate tissue use of oxygen
Explain the dissociation of carbonic acids into bicarbonate and hydrogen ions.
Carbonic acid (in RBC, H2CO3) dissociates into hydrogen and bicarbonate ions (H+ and HCO3-) = Faster with carbonic anhydrase o About 70% CO2 transported to lungs from tissue • H+ combine with Hgb (powerful acid-base buffer)
What ocurrs at the BBB with H+ and CO2 to stimulate respiration?
Effect of blood PCO2 in stimulating the chemosensitive area
- CO2 + H2O → carbonic acid → HCO3- + H+ → H+ after CO2 has diffused across BBB
- Chemosensitive region is stimulated much more rapidly if the CO2 enters via the CSF rather than the brain interstitial water (less protein buffers for the hydrogen in the CSF)
- The excitation of the respiratory center to the increased CO2 is great within the first few days but subsequently declines over the next 1-2 days
o Due to renal compensation for acidosis by retaining bicarb, AND bicarb diffusing across BBB to buffer H+ there
How does alveolar ventilation occur?
• Alveolar ventilation: rate at which air reaches the gas-exchange regions
o The gas in the air really only goes down to the terminal bronchioles and not into the alveoli during normal inspiration. It makes it the rest of the way by simple diffusion.
How does oxygen reversibly bind to hemoglobin?
O2 combines loosely/reversibly with heme portion of hemoglobin
o PO2 high = O2 binds to hemoglobulin (pulmonary capilaries)
o PO2 low = O2 is released (tissue capilaries)
How many molecules of oxygen can be bound by 1 Hemoglobin?
4 molecules of Oxygen per 1 Hb
Name 5 major categories of hypoxemia?
Extrinsic problems •
- Low FIO2 (high altitude) •
- Hypoventilation (neuromuscular disease) Pulmonary disease • 2. Hypoventilation (increased airway resistance, decreased lung compliance) •
- Diffusion impairment •
- V/Q mismatch o High V/Q: physiologic dead space o Low V/Q: physiologic R-L shunt Anatomic shunts •
- Right-to-left cardiac shunts Inadequate O2 transport to tissues •
- Anemia or abnormal Hgb •
- Hypovolemic shock Inadequate capability of the cells to use oxygen (uncoupling of oxidative phosphorylation) •
- Metabolic abnormalities, cyanide toxicity
Name the 4 major factors that will shift the oxygen-hemogloblin dissociation curve to the right.
Situations when there is a decreased affinity of Hb to oxygen → Unloading of O2 (great in tissue)
- Increased PCO2
- Decreased pH (more acidic)
- Increased temp
- Increased 2,3-DPG (byporduct of glycolysis)
Name the factors that can affect the oxygen-hemoglobin dissociation curve?
• pH Changes:
o Acidic (7.4 → 7.2): Shifts curve to right (about 15%)
o Basic (7.4 → 7.6): Shifts curve to left
- ↑ CO2 concentration → Shifts curve to right
- ↑ Blood Temperature → Shifts curve to right
- ↑ 2,3-biphosphoglycerate (BPG) → Shifts curve to right
o Phosphate compound in blood
Parasympathetic stimulation to airways leads to ….
Bronchoconstriction via acetylcholine release (muscarinic)
Sympathetic stimulation to airways leads to…..
Bronchodilation (B2 adrenergic)
What are factors that affect the diffusion of gas through the respiratory membrane?
- Thickness of membrane (edema, fibrosis)
- Surface area of membrane (↓ by lung removal, emphysema)
- Diffusion coefficient of gas in membrane (CO2 20x faster than O2)
- Partial pressure difference of gas btwn 2 sides of membrane (PP> alveoli than in blood (O2)
Net diffusion from alveoli into blood
PP> blood (CO2), net diffusion from blood to alveoli)
What are the effects of emphysema and pulmonary fibrosis on lung compliance?
Emphysema = Increased lung compliance (loss of elastic fibers) Pulmonary Fibrosis = Decreased lung compliance (increased stiffness of the lungs)
What are the layers of the respiratory membrane?
o Layer of fluid lining alveolus (containing surfactant: surface tension of alveolar fluid)
o Alveolar epithelium composed of thin epithelial cells o Epithelial basement membrane
o Thin interstitial space btwn alveolar epithelium and capillary membrane
o Capillary basement membrane (fuses with alveolar epithelial basement membrane)
o Capillary endothelial membrane
What are the main forms that CO2 travels in the body?
- Dissolved in solution
- Bicarbonate (Major form)
- Combined with hemogloblin (o CO2 reacts with water, amine radicals of Hgb → carbaminohemoglobin (CO2Hgb)
o Reversible reaction – slow!!
o Only small amount of CO2 reacts this way (1/4th quantity of Hgb)
o Carbamino + Hgb and plasma protein: 30% total amount transported
What are the two extremes of V/Q mismatches?
Ventilation-perfusion ratio (V/Q): Respiratory exchange when imbalance btwn alveolar ventilation and alveolar blood flow
o No exchange f gases V/Q = 0 → Ventilation zero, yet there is still perfusion V/Q = infinity →Ventilation adequate, but zero perfusion
What are the two qualities controlled in the inspiratory ramp?
- Rate of increase of ramp signal
- Limiting point at which ramp stomp sudddenly decreases
Rate of increase of ramp signal - during heavy respiration, ramp increases rapidly, fills the lungs rapidly
Limiting point of ramp cessation - earlier ramp ceases the shorter the duration of inspiration – and ultimately, increases respiration frequency.
Ramp - weak and stead increase of action potential to inspirator muscle, then ceases.
What controls the mechanism of pulmonary hypoxic vasconstriction?
Direct action of alveolar PO2 on the vascular smooth muscle of pulmonary arterioles
HYPOXIC pulmonary vasoconstriction (HPV) is a reflex contraction of vascular smooth muscle in the pulmonary circulation in response to low regional partial pressure of oxygen (Po2). This vasoconstriction by the pulmonary vasculature represents its fundamental difference from the systemic circulation, which typically vasodilates in response to hypoxia.
What determines tissue PO2?
Tissue PO2 determined by rate of O2 transport to tissue in blood and rate at which O2 is used by tissues
What does the sigmoidal shape of the oxygen-hemoglobin curve reflect?
Increased affinity for each successive molecule of O2 that is bound
What drives the mechanism for hypoxic pulmonary vasoconstriction?
a. Central chemoreceptors detect low arterial PO2 –> systemic catecholamines –> constriction of smooth muscles in small arterioles of hypoxic region
b. Central chemoreceptors detect low arterial PO2 –> systemic vasoactive substances (nitric oxide, endothelin-1) –> constriction of smooth muscles in small arterioles of hypoxic region
c. Low alveolar PO2 causes changes in local perivascular tissue –> local catecholamines –> constriction of smooth muscles in small arterioles of hypoxic region
d. Low alveolar PO2 causes changes in local perivascular tissue –> local vasoactive substances (nitric oxide, endothelin-1) –> constriction of smooth muscles in small arterioles of hypoxic region
D. Low alveolar PO2 causes changes in local perivascular tissue –> local vasoactive substances (nitric oxide, endothelin-1) –> constriction of smooth muscles in small arterioles of hypoxic region
Everything here happens locally. Get clinical improvement with inhibitors of NO synthase and blockers of endothelin receptors.
What effect does anemia have on the O2 saturation curve?
a. Shifts it upwards
b. Shifts it downwards
c. Shifts it to the left
d. Shifts it to the right
B = Shifts it downward - there is less oxygen carrying capacity in the blood overall, therefore at ALL PO2 values along the x axis will not pick up as much O2, so the O2 concentration on the y axis is lower. See the attached pic.
Upward shift caused by Polycythemia (opposite of anemia) - Increased oxygen carrying capacity overall.
- Right shift caused by increased H+, increased PCo2, increased temp- aka all the things that increase with exercise. Also increased 2,3 DPG with chronic hypoxia, high altitude, chronic lung diz. Right shift = increased unloading at peripheral tissues.
- Left shift caused by low H+, low PCO2, low temp. Also low 2,3 DPG from prolonged storage in blood bank. Left shift = increased uptake at lungs.
What graph is used to assess the compliance of the lungs?
Pressure-volume loops - The slope of each line is the compliance of the lung itself
What happens in the peripheral chemoreceptors when O2 falls below 60 mmHg?
When the pO2 falls below 60 mm Hg, nerve impulses from the carotid body increase rapidly and respiration increases
- Stimulation by low PO2 may occur via glomus cells in bodies → synapse with nerve endings (or may be direct sensitivity of nerve endings to O2)
- Increased CO2 and H+ also activate chemoreceptors; this effect is much less in magnitude than their direct effect, but occurs more rapidly
What happens when there is left shift in the oxygen-hemogloblin dissociation curve?
There is an increased affinity of Hb to oxygen → Harder to unload O2 (great in lungs)
What is Cheyne-Stokes breathing?
o Characterized by slowly waxing and waning respiration, occurring over and over again about every 40-60 secs o The basic cause is due to transient overbreathing: 1. Blow off too much CO2 → delay before changed pulmonary blood can be transported to brain and inhibit excess ventilation 2. When overventilated blood eventually reaches the brain, the center becomes depressed an excessive amount → CO2 increases in alveoli → again takes brain delay before it catches up
What is expiratory reserve volume?
Expiratory reserve volume → extra amount of air that can be expired by forceful expiration after the end of a normal tidal expiration
What is functional residual capacity?
Functional residual capacity → expiratory reserve volume + residual volume • This is the amount of air that remains after normal expiration.
What is inspiratory capacity?
Inspiratory capacity → equals the tidal volume + inspiratory reserve volume • The amount of air a person can breathe beginning at the normal expiratory level and distending the lungs to the maximum amount.
What is inspiratory reserve volume?
Inspiratory reserve volume → extra volume of air that can be inspired over and above the normal tidal volume
What is residual volume?
Residual volume → volume of air remaining in the lungs after the most forceful expiration
What is surfactant?
Used to greatly reduce surface tension, is produced by Type II alveolar epithelial cells (pneumocytes).
What is the Bohr Effect in regards to the oxygen-hemoglobin dissociation curve?
Shift of curve to right (due to ↑ CO2 or ↑ Hydrogen ions)→ Significant enhancement of release of O2 from blood into tissues, enhancing oxygenation of blood in lungs → Bohr Effect o Blood passes through tissue: CO2 diffuses from tissue cells to blood → ↑ blood PCO2 → ↑ blood H2CO3 (carbonic acid) and hydrogen ions → Shifts curve to right and downward → forcing O2 away from Hgb and thus delivering ↑ O2 to tissues o Lungs: CO2 diffuses from blood into alveoli → ¯ blood PCO2 → ¯ hydrogen ions → Shifts curve to left and upward → Greater binding of O2 to Hgb at any given alveolar PO2
What is the chloride shift in RBCs?
• Many ions diffuse from RBCs into plasma (Cl takes their place in RBCs = bicarbonate-chloride carrier protein → 2 ions in opposite directions o Cl content of RBCs greater in venous than arterial RBCs → Chloride Shift (phenomenon)
What is the difference between anatomic and physiologic dead space?
• Physiological dead space → equal to the number of alveoli not participating in gas exchange • Anatomic dead space → refers solely to those airways not participating in gas exchange whereas physiologic dead space is equal to the anatomic dead space plus the non-functional alveoli (anatomic and physiologic dead space or nearly equal in healthy patients)
What is the equation for forming bicarbonate from CO2?
CO2 + H2O → (carbonic anhydrase) H2CO3 → H+ + HCO3-
What is the function of the nose?
Air is warmed, humidified, and filtered. Turbulent filtration occurs as the air hits the turbinates and must change direction
What is the greatest resistance to passage of air in a normal patient?
The resistance of the large airways
What is the Haldane Effect?
o ↑ CO2 in blood causes O2 to be displaced from Hgb (Bohr effect) o Important factor for ↑ O2 transport o Opposite true: Binding of O2 with Hgb tends to displace CO2 from blood (Haldane effect) More important at promoting CO2 transport than the Borh effect is at promoting O2 transport Combination of O2 with Hgb in lungs causes Hgb to become a stronger acid • Displaced CO2 from blood into alveoli: 1. More highly acidic Hgb has less tendency to combine with CO2 to form carbaminohemoglobin (displacing more CO2 that is present in carbamino form in blood) 2. ↑ Acidity of Hgb causes release of excess Hydrogen ions and binds with bicarbonate to form carbonic acid (dissociated in water and CO2 and CO2 is releases from blood into alveoli into air)
What is the Hering-Breuer inflation reflex?
o Lung inflation signals limit inspiration (Hering-Breuer inflation reflex) Stretch receptors in the lungs transmit signals via the vagus nerve to the dorsal respiratory group to limit inspiration when the lungs are full of air Similar to the pneumotaxic center in that it switches off the inspiratory ramp = inhibits inspiration (but increases the respiratory rate) when the lungs are full
What is the intrapleural pressure?
It is negative pressure (opposing forces of the lung trying to collapse and the chest wall trying to expand
What is the most important component of surfactant?
DPPC (dipalmitoyl phosphatidylcholine) - based on amphipathic nature of phospholipid (hydrophobic on one end and hydrophilic on the other end) - Reduces surface tension depsite small radius on alveoli
What is the normal direction of fluid flow in the pulmonary capillaries?
The normal outward forces of the capillary are just slightly greater than the inward force and so fluid constantly leaks into the interstitium (pumped back into circulation through lymphatics through slight negative interstitial pressure)
What is the oxygen-hemoglobin dissociation curve?
↑ % Hemoglobin bound as PO2 ↑ = percent saturation of hemoglobin o When PO2 = 95 mmHg → 97% bound to Hgb o When PO2 = 40 mmHg (tissues) → 75% bound to Hgb
What is the rate of alveolar ventilation?
Alveolar ventilation per minute is the total amount of new air entering the alveoli per minute. It is equal to the amount of new air that enters the alveoli X the respiratory rate (Va=RR X (Vt-Vd)) • Vd = dead space • Vt = tidal volume
What is the result of histamine in the airways?
Bronchiole constrictions (works locally)
What is the role of CO2 in controlling respiration?
Excess carbon dioxide or H+ ions → stimulate the respiratory center directly to increase strength of inspiration and expiration • Hydrogen ions are the only important stimulus for the chemosensitive area • However, H+ do not readily cross the BBB or Blood-CHSF barrier; thus CO2 ends up being more important
What is the role of hemogloblin in oxygen transport?
• 97% O2 carried on hemoglobin in RBCs • 3% O2 dissolved in water in plasma and blood cells
What is the role of O2 in controlling respiration?
Oxygen → no direct effect on respiratory center; acts on peripheral chemoreceptors in carotid and aortic bodies → signals to respiratory center
What is tidal breathing?
Tidal volume → volume inspired or expired with each normal breath
What is total lung capacity?
Total lung capacity →Equals the vital capacity + residual volume • Maximal volume to which the lungs can be expanded with the greatest possible inspiratory effort
What is typically the percent saturation of systemic arterial blood?
97% (95 mmHg)
What is typically the percent saturation of venous blood?
75% (40 mmHg)
What is vital capacity?
Vital capacity → inspiratory reserve volume + tidal volume + expiratory reserve volume • This is the maximum amount of air a person can expel from the lungs after first filling the lungs to their maximal extent and then expiring to their maximal extent
What Law governs the diffsuion of O2 and CO2 across membranes?
Fick’s Law of Diffusion (driven by partial pressures difference of the gas)
What occurs in automatic control of pulmonary blood flow distribution?
Decreased oxygen concentration in the alveoli (less than 73 mmHg PO2) results in vasoconstriction of the surrounding vessels →shunting blood away from the hypoxic alveoli. • This is the opposite of what occurs in the other vascular beds
What stimulates ventilation during exercise?
Chemical signals ARE NOT the stimulus for increased respiration during exercise (they are normal!) 1, Instead, brain higher functions send collateral messages to the respiratory centers (while they are sending messages to muscles to stimulate contraction) 2. Movements of the limbs stimulates joint and muscles proprioceptive receptors that transmit impulses to the DRG to stimulate ventilation
Where is carbonic anyhdrase found in high concentrations?
In RBCs Aids in transport of CO2 in blood
Where is the expiratory center in brain?
Ventral respiratory center
Where is the inspiratory center in brain?
Dorsal respiratory center
Why does administration of 100% oxygen NOT improve hypoxemia during shunting?
a. Worsens vasoconstriction + shunting, therefore worsening the degree of shunting in the lungs
b. Not true - it DOES improve hypoxemia during shunting.
c. Depresses respiratory drive, causing decreased respiratory rate and worsening hypoxemia
d. The shunted blood does not get exposed to ventilated alveoli and the blood exposed to ventilated alveoli is already saturated.
D .. Usually increases respiratory drive because the chemoreceptors detect increased arterial PCO2 from the shunted blood and icnrease the ventilation. This lowers PCO2 but has no effect on the PO2.
What is vital capacity?
The exhaled volume after a maximal inspiration
What is tidal volume?
The amount of air entering the lung while breathing
Which of the following does not shift the oxygen dissociation curve to the right?
a. Acidemia
b. Hypercapnia
c. Hypothermia
d. Increased 2,3-diphosphoglycerate
c. Hypothermia
Would you use bronchodilators to treat a case of ALI/ARDS?
No! It can worsen the V/Q mismatch
