Pulmonary Flashcards

Question

Obstructive Lung Disease

Answer 1

Allows air to enter the lungs but makes expiration difficult. Ex. emphysema, bronchitis, and bronchiectasis. Both FEV₁ and FVC are reduced. FEV₁ reduced to a greater extent. FEV₁ / FVC ratio decreased.

Answer 2

Makes inspiration difficult but do not affect expiration. Ex. fibrosis, bronchitis, and respiratory distress syndrome (due to surfactant deficit or lung injury). FEV₁ and FVC reduced to more or less the same extent. FEV₁ / FVC ratio is normal or sometimes increased.

Answer 3

**Active Process** 1. During tial breath, **diaphragm** controlled by the **phrenic nerve** contracts 2. Abdomen pushed downward and forward 3. Ribs lifted and moved out 4. During forced inspiration/exercise, additional muscles such as the **external intercostal muscle** recruited 5. All serves to increase transverse diameter of the thorax 6. P_pl and P_A becomes more negative drawing air in.

Answer 4

**Passive process** during quiet breathing. **Active process** during forced expiration. 1. **Diaphragm** relaxes. 2. **Chest wall** and **lung** return to equilibrium positions. 3. P_pl becomes less negative and P_A become positive. Air is moved out. 4. During forced expiration/exercise, additional muscles such as **abdominal muscles** and **internal intercostal muscles** contract. 5. P_pl becomes positive (only time). Air forced out at greater rate.

Answer 5

As P_pl becomes more negative and P_A falls below atmospheric pressure, the lungs will expand. **Volume** measured with spirometry as a function of **pressure**. Slope of the curve represents **compliance**.

Answer 6

Pulmonary pressure-volume curves during inflation and deflation are different. Mostly due to differences in compliance. Lung volume at any given pressure during deflation is larger than during inflation.

Answer 7

C = ΔV / ΔP * In the normal range of expanding pressures (-5 to -10 cm H₂O): * Lung very compliant * P-V curve steep * As expanding pressures get higher: * Lung becomes stiffer due to elastic recoil * Seen as flattening of the P-V curve at higher expanding pressures * During deflation, lungs start at a lower compliance state: * Deflation curve starts out flat

Answer 8

1. **Surface tension** decreases compliance 2. **Fibrosis** decreases compliance * seen in restrictive disorders 3. **Alveolar edema** decreases compliance * excess fluid accumulation in the lungs 4. **Increased pulmonary venous return** reduces compliance * excess blood accumulation in the lungs * seen in heart failure 5. **Loss of elastic tissue** increases compliance * seen with emphysema or aged lungs

Answer 9

Restrictive diseases decrease lung compliance. Results in narrowing of the PV-loop. Obstructive diseases increase lung compliance. Results in widening of the PV-loop.

Answer 10

**Chest wall** elastic recoil **pulls outward**. _Greater at low lung volumes_. Tendency for the lung to expand indicated as _negative transmural pressure._ **Alveoli** elastic recoil **pulls inward**. _Greater at high lung volumes_. Tendency for the lung to collapse indicated as _positive transmural pressure._ Combined pulmonary compliance is the sum of the two. At **FRC**, lung elastic recoil = chest elastric recoil so **transmural pressure ⇒ 0**.

Answer 11

Chest wall compliance remains constant. Pulmonary diseases **affects compliance of the lung**. **Alters equilibrium point** of the lung and chest wall. _Obstructive disorders_ **increase** compliance & equilibrium point (i.e. FRC). _Restrictive disorders_ **decrease** compliance & equilibrium point (i.e. FRC).

Answer 12

Thin liquid film coats each alveolus affecting the P-V relationship. Molecules of liquid more attracted to each other than to gas accounting for surface tension. Saline-filled lung more compliant than air-filled lung = no hysteresis. Foam from pulmonary edema with tiny air bubbles extremely stable = low surface tension.

Answer 13

Pressure (P) required to keep an alveolus of radius (r) open affected by surface tension (T). **P = 2T / r** If surface tension constant, pressure in smaller alveolus greater than in larger one. Pressure gradient drives air from smaller to larger alveolus causing collapse of the smaller alveolus ⇒ **atelectasis**. Common at lower lung volumes.

Answer 14

Lipid/protein mixture secreted by Type II pneumocytes. Mostly dipalmitoyl phosphatidylcholine (DPPC). **Alters the surface tension with changes in diameter.** * Surfactant density increases with lung deflation ⇒ reduces surface tension ⇒ decreases pressure * Lowers surface tension to a greater extent in smaller alveoli * Prevents atalectasis **Increases lung compliance.** * As lung inflates, surfactant / area decreases * Compliance will decrease as lung inflates * Partially accounts for flattening of the inflation curve at high volumes **Helps prevent pulmonary edema.** * Surface tension promotes fluid movement from capillaries to alveolar spaces. * Surfactant decreases surface tension preventing movement of fluid into alveoli.

Answer 15

* Surfactant production starts ~ 34 weeks gestation * Insufficiency seen with premies * Difficulty in inflating lungs due to high surface tension * Treat with CPAP and exogenous surfactant until neonate able to synthesize enough

Answer 16

**Compliance is greater at the base of the upright lung than the apex.** * Gravity causes weight of the lung to pull down on the alveoli. * P_pl more negative at apex compared to base. * Alveoli at the apex more inflated at rest. * Apex rests at higher point on compliance curve than base. * Alveoli at the base inflate more easily

Answer 17

1. **_Before inspiration:_** * P_pl negative due to elastic recoil of lung * P_A = 0 * No airflow 2. **_Inspiration:_** * P_pl more negative due to diaphragm contraction * P_A becomes negative * Alveoli mechanically tethered to chest wall * Pressure difference draws air in * Alveoli expand ⇒ P_A increases ⇒ stops becoming more negative ⇒ still subatmospheric so airflow continues 3. **_End of Inspiration / Beginning of Expiration:_** * P_pl more negative * P_A = 0 * No airflow 4. **_Expiration:_** * Breathing muscles relax * Alveolar elastic recoil high * P_pl becomes less negative * P_A starts to become positive * Air flows out of alevoli

Answer 18

Airway diameter main determinant of airflow. Main site of resistance in the intermediate-sized airways. Governed by Poiseuille's Law and Ohm's Law:

Answer 19

1. **Lung Volume** * Higher volume ⇒ airway opened ⇒ greater diameter ⇒ decreased resistance 2. **Bronchial Smooth Muscle** * ANS ⇒ vagus nerve ⇒ Ach ⇒ β₂-adrenergic receptors ⇒ bronchodilation ⇒ decreased resistance * Albuterol = β₂-adrenergic agonist

Answer 20

**Flow rate is independent of effort towards low lung volumes.** * During forced expiration, flow rate declines as more air expired. * Occurs whether expiration starts with maximal effort or slowly and accelerates * Due to airway compression by increased P_pl

Answer 21

1. **_Pre-inspiration (A)_** * Pleural pressure (P_pl) = -5 cm H₂O * Alveolar pressure (P_A) = 0 * Transairway pressure (P_L) = +5 cm H₂O 2. **_Beginning of Inspiration (B)_** * Diaphragmatic contraction causes both P_pl and P_A to become -2 cm H₂O more negative * Airflow causes 1 cm H₂O pressure drop in airway * P_L = +6 cm H₂O 3. **_End of Inspiration (C)_** * P_A = O * P_PL = -8 cm H₂O * P_L = +8 cm H₂O 4. **_Forced Expiration (D)_** * Both P_pl and P_A increase by +38 cm H₂O * Outward airflow causes a pressure drop along the airway * P_L drops along the airway until P_pl = P_A * When P_L = 0 ⇒ equal pressure point * Negative P_L beyond this point ⇒ tendancy to close airway * EPP in healthy person occurs at a point high enough where cartilage present and prevents closure * As expiration continues, EPP moves deeper into lung

Answer 22

* Emphysema causes loss of alveoli and elastic recoil * Lowers P_A further during forced expiration * Pushes EPP lower in the lung * Causes airway to collapse closer to alveoli where cartilage not present * Results in difficulty with expiration ⇒ hyperinflated lungs ⇒ barrel chest * Breathing through pursed lips inc. resistance at the mouth causing a pressure drop * Moves EPP back up to conducting zone

Answer 23

Airway resistance stable during quiet breathing. Forced expiration causes compression of airways resulting in greater airway resistance. **Flow-volume loops** generated by: 1. Inhale to TLC 2. Forced expiration to RV as quickly and forcefully as possible 3. Forcibly inhale back to TLC Upper part of the loop is the flow-volume curve. Can be used to detect various types of airways diseases.

Answer 24

* **_Restrictive Disorders_** * Lung fills to **lower** volume. * Maximum flow rate decreased. * Total volume exhaled reduced. * **_Obstructive Disorders_** * Lung fills to a **greater** volume. * Maximum flow rate decreased. * Total volume exhaled reduced.

Answer 25

**P_Igas = F_Igas x P_B** P_Igas = partial pressure of the inspired gas F_Igas = fraction of that gas in total mixture P_B = barometric pressure (760 mmHg @ sea level) The **total pressure** of a gas mixture is equal to the **sum of the partial pressure of each gas**. Each gas exerts a partial pressure that is **proportional to its concentration** and **independent** **of the other gases**.

Answer 26

Conducting zones warm and humidify air so it contains water vapor when it reaches the alveoli. Partial pressure water vapor at 37° is **47 mmHg**. Taken into account via modied Dalton's Law: **P_Igas = F_I_gas x (P_B - P_H2O)**

Answer 27

The amount of air that enters per minute. (mls/min) **V̇_E = B*_f* x V_T** B*_f* = breathing frequency (breaths/min) V_T = tidal volume

Answer 28

* **Anatomic dead space** * Volume of air which remains in the conducting zone and is unavailable for gas exchange. * Normal ~ 150 mls * **Alveolar dead space** * Volume of functional dead space which is unable to participate in gas exchage due to pathological process * Ex. poor perfusion * **Physiological dead space (V_D)** * Anatomical dead space + alveolar dead space * Normally, V_D = anatomic dead space

Answer 29

**Physiological dead space** determined using **partial pressure of CO₂** in **alveolar gas** (P_ACO2) and **expired gas** (P_ECO2). Assumptions: No CO₂ in inspired gas. All of the CO₂ in expired gas comes from the alveoli. Because P_CO2 in alveolar gas virtually identical to arterial P_CO2 in healthy individuals, values from standard blood gas measurements used.

Answer 30

V̇_A = B_f x (V_T - V_D) The amount of gas that actually makes it to the alveoli and is available for gas exchange.

Answer 31

* Two main ways of altering alveolar ventilation: 1. **Breathing frequency (B_f)** 2. **Volume inspired** * Dead space constant under normal conditions. * Alveolar ventilation is best increased by increased tidal volume. * Hyper-respiration essentially moving air in and out of conducting zones without inspiring fresh air into lungs.

Answer 32

Alveolar ventilation rate can be estimated without knowing the dead space volume.

Answer 33

If rate of CO₂ production is constant: **Alveolar ventilation rate is inversely proportional to alveolar (and arterial) P_CO2.** * Decreased B_f results in hypercapnea. * Hyperventilation is a physiological response to hypercapnia. * If CO₂ production increases, alveolar ventilation will increase to paintain a constant P_a_CO2.

Answer 34

Relationship between P_AO2, P_ACO2, and the rate of CO₂ generation and O₂ consumption. Estimates alveolar O₂ levels using easily obtained parameters. * **P_IO2** = O₂ partial pressure in moist inspired air * **R** = respiratory quotient * amount of CO₂ relative to O₂ consumed in one breath * R = 0.8 for typical diet with carbs and fats * **F** = correction factor * ~ 2 mmHg * often ignored * Arterial CO₂ used as surrogate for alveolar CO₂

Answer 35

Ventilation is the highest at the base of the lung and lowest at the apex. * Gravity causes a more negative pleural pressure at the apex compared to base. * Top is already partially inflated and can inflate less upon inspiration. * Bottom somewhat compressed and can expand more upon inspiration. * Determined using radioactive ¹³³Xe

Answer 36

* Low resistance, low pressure system * Pulmonary vascular resistance (PVR) ~ 1/10th of systemic circulation * Pulmonary arteries less elastin and smooth muscle * Pulmonary arterioles thin-walled and less smooth muscle * Less ability to constrict compared to systemic arterioles * Pulmonary capillary beds form mesh-like network * Blood flows as a sheet over alveoli

Answer 37

**Inc. CO ⇒ Inc. pulmonary arterial pressure ⇒ Dec. PVR ⇒ Inc. blood flow.** Due to two mechanisms: 1. **Recruitment of capillaries** * Some capillaries partially or fully closed at rest * Particularly at the top due to low perfusion pressure * As CO increases, vessels "inflate" to decrease PVR * Added in parallel 2. **Distention of capillaries** * Increases diameter of the vessels lowering PVR **Recruitment precedes distension.**

Answer 38

**Extra-alveolar vessels** affected by **pleural pressure**. **Alveolar vessels** affected by **alveolar pressure**. * **_High lung volumes:_** * Pleural pressure most negative * **Extra-alveolar vessel resistance at minimum** * Alveolar volume/pressure is highest * **Alveolar vessel resistance at maximum** * **_Low lung volumes:_** * Pleural pressure less negative * **Extra-alveolar vessel resistance at maximum** * Alveolar volume/pressure is lowest * **Alveolar vessel resistance at minimum** **** **Total resistance** of the circulation is the combination of both types of vessels. **Lowest resistance at FRC.**

Answer 39

**PVR increased by alveolar hypoxia or hypoxemia.** Hypoxia induces vasoconstriction of small pulmonary arteries. Two types of alveolar hypoxia can occur: 1. Regional hypoxia: * vasoconstriction localized to a region * useful in shifting blood away from poorly-ventilated alveoli * does not usually cause increased PVR due to parallel pulmonary capillaries 2. Generalized hypoxia: * vasoconstriction throughout lungs * increased PVR * occurs in low oxygen environments * can lead to pulmonary edema * can result in right-sided hypertrophy and heart failure

Answer 40

Forces regulating pulmonary capillary fluid flow: 1. Starling forces: * **Capillary hydrostatic pressure** ⇒ fluid out * **Capillary oncotic pressure** ⇒ fluid in * **Interstitial hydrostatic pressure** ⇒ fluid out ⇒ ~ 0 * **Interstitial oncotic pressure** ⇒ fluid in 2. **Surface tension** * Pulls inward lowering interstitial hydrostatic pressure (P_i) * Help to draw fluid into interstitial space 3. **Alveolar pressure** * Compresses interstitial space increasing interstitial hydrostatic pressure * Helps prevent fluid from leaving capillary **Normally, net movement of fluid is from the alveoli to the interstitial space.** Removed by the lymphatic system.

Answer 41

1. **_Increased capillary hydrostatic pressure_** * Due to increased pumonary venous pressure * Heart failure * Mitral valve stenosis 2. **_Increased capillary permeability_** * pulmonary vascular injury * inflammation * neurogenic shock 3. **_Increased surface tension_** * Loss of surfactant * Adult respiratory distress syndrome

Answer 42

**Pulmonary blood flow greatest at the base.** Due to relationship between **pulmonary artery pressure, alveolar pressure, and pulmonary vein pressure** caused by gravity. Creates 3 **functional zones** of the lung: * **Zone 1**: P_A \> P_a \> P_v * Alveolar pressure greater than arterial pressure * Collapses blood vessels * Allows no blood flow * Absent under normal condition * Can occur with: * positive pressure ventilation * low pulmonary blood flow (ex. hemorrhage) * **Zone 2:** P_a \> P_A \> P_v * Arterial pressure greater than alveolar pressure * Blood flow determined by difference between P_a and P_A * Occurs in the **middle of the lungs** * As we move further down into the lung: * P_a increases while P_A stays fairly constant * Pressure difference increases ⇒ inc. pulmonary blood flow through **recruitment** * Continuous increase in pressure difference as one moves down the lungs ⇒ **waterfall effect** * **Zone 3:** P_a \> P_v \> P_A * Venous pressure greater than alveolar pressure * Blood flow dictated by **difference between P_a and P_v** * Inc. in pulmonary blood flow due to **distention**

Answer 43

1. Reservoir of blood 2. Filter out small thrombi 3. Secretion of mucous as a protective system 4. Metabolic functions * Activation of Ang I → Ang II * Inactivation of many vasoactive substances

Answer 44

* **_Normal conditions (A)_** * Alveolar gas content between between venous and atmospheric * O₂ entering * CO₂ leaving * **_Airflow blocked / Perfusion normal (B)_** * No ventilation (V=0) * **V/Q ratio = 0** * Blood equilibrates with gases in alveoli * Alveolar gas similar to venous blood gas values * Low O₂ * High CO₂ * **_Airflow normal / No perfusion (C)_** * Q = 0 * **V/Q ratio = ∞** * Alveolar gas similar to atmospheric air * High O₂ * No CO₂ **As V/Q ratio increases, P_AO2increases and P_ACO2 decreases.**

Answer 45

Both ventilation and perfusion greatest at the base. Perfusion varies to a greater extent. **V/Q ratio will vary along the height of the lung with greatest value at the apex.** Between 0.5 and 2.5.

Answer 46

Alveolar gas composition varies along the height of the lung. **Highest P_AO2 and lowest P_ACO2 at the apex.** Due to regional V/Q variations.

Answer 47

Lung is not as efficient at oxygenating arterial blood due to uneven V/Q ratios. **Apex with higher P_AO2 (~ 132 mmHg) but lower perfusion.** **Base with lower P_AO2 (~89 mmHg) but greater perfusion.** Majority of the blood leaves from the base. **Arterial blood has values closer to that of the base than the apex.**

Answer 48

**_Normal (Left)_** * Ventilation and perfusion more or less matched * Majority of ventilation and blood flow goes to regions with V/Q ratio ~ 1 **_COPD_** * Much of the ventilation and blood flow associated with normal V/Q ratios ~ 1 * **Significant blood flow associated with areas with V/Q \<\< 1** * Ineffective movement of O₂ into and CO₂ out of the blood * Alveolar & arterial P_O2 low ⇒ **hypoxia** * Alveolar & arterial P_CO2 high ⇒ **hypercapnea** * Depresses overall P_aO2 returning to systemic circulation * Compensate by **increasing ventilation to other regions** * Results in **V/Q ratios greater than normal** * Due to insuffient blood flow, regions may be ineffective at eliminating CO₂ * Increased ventilation to compensate for hypercapnea * Not as effective for oxygen due to dissociation curves * **Results in normal P_a_CO2 but arterial hypoxia**

Answer 49

**The difference between alveolar and arterial oxygen concentrations** **Normal A-a gradient ~ 5-15 mmHg.** P_AO2 = ~ 100 mmHg and P_a_O2 = ~ 85-95 mmHg * In a healthy person due to: 1. Regional V/Q variations 2. Mixing of venous blood with arterial blood due to anatomical shunts (~1-2% of total blood) * _Bronchial circulation_ drains into _pulmonary vein_ * _Coronary venous blood_ drains directly into left ventricle via _Thebesian veins_ * A-a gradient determined using: * Measurements of arterial blood gasses (P_aO2 and P_aCO2) * Alveolar gas equation to determine P_AO2

Answer 50

Defined as P_aO2 \< 85 mmHg. A-a gradient and response to O₂ therapy can distinguish among the 4 types of respiratory causes. * _Respiratory causes_ * regional hypoventilation * generalized hypoventilation * larger than normal anatomic shunt * diffusion block across blood-gas barrier * _Non-respiratory causes_ * reduced O₂ content of inspired air

Answer 51

Describes the diffusion of gases across the blood gas barrier: * A = area for diffusion * T = thickness of diffusion path (~0.3 µm in blood-gas barrier) * D = diffusion coefficient * proportional to solubility * inversely proportional to sq. rt of MW * (P₁ - P₂) = partial pressure gradient of gas

Answer 52

1. **Emphysema** * Destruction of alveoli * Decreased SA for gas exchange 2. **Pulmonary edema** * Inceases thickness of path gas must traverse 3. **High altitudes** * Decreases barometric pressure * Reduced P_IO2 4. **Cardiac output** * Changes transit time of RBC through pulmonary circulation * Unlikely to change CO so much that equilibrium does not occur

Answer 53

**Perfusion-limited gas** * Diffuses across blood-gas barrier * No affinity for hemoglobin * Partial pressure rises in blood rapidly * Equilibrates between blood and alveoli quickly * No additional diffusion occurs d/t no gradient * Only way to increase amount absorbed is to increase blood flow

Answer 54

**Diffusion-Limited Gas** * Diffuses through alveolar-capillary membrane * Strong affinity for hemoglobin * Essentially all of it rapidly binds to Hb * P_aCO ~ 0 * Partial pressure gradient never becomes 0 * Driving force present throughout entire RBC transit time * Diffusion-limited gas but not limited by blood flow

Answer 55

**Perfusion-limited** * Diffuses across blood-gas barrier * Affinity for hemoglobin * Equilibrates in blood in ~ 0.25 sec * RBC transit time ~ 0.75 sec * Normally perfusion-limited * Some diseases can cause thickening of interface effecting kinetics of O₂ uptake * Measure diffusing capacity

Answer 56

Rate of gas transfer relative to a partial pressure gradient. **Diffusing capacity (D_L) = AD/T** Fick's Law becomes: **V̇ = D_L x (P₁ - P₂)**

Answer 57

**D_LCO = V̇_CO / P_ACO** * Measures rate of CO disappearance in alveolar gas. * CO diffusion-limited so **partial pressure gradient is P_ACO**. * Provides information about the **integrity of the alveolar-capillary surface for gas exchange**. * _Pulmonary fibrosis_ * Increases thickness of alveolar wall * Decreases in D_LCO * _Decreased hematocrit_ * Fewer RBC arriving at the lungs * Decreases D_LCO

Answer 58

_O₂ transported in the blood in two forms:_ ## Footnote **Dissolved in blood (2%)** **Bound to hemoglobin (98%)**

Answer 59

Amount of oxygen dissolved in the blood: **[O₂] = 0.003 x P**_O2 0.003 ⇒ solubility constant for O₂ in the blood at 37° (ml O₂/dL-mmHg) Concentration of O₂ (ml O₂/dL blood)

Answer 60

* **% saturation of Hb with O₂** (S_aO2) * ratio of oxygen content to capacity * **Oxygen content** ([HbO₂]) * the _actual_ amount of O₂ bound to hemoglobin * most important guage for oxygenation * normal ~ 20 ml / 100 ml * **Oxygen-carrying capacity** ([HbO₂]_max) * maximal capacity for Hb to carry O₂ in the blood * assuming normal Hb concentration is ~ 20.1 ml O₂/dL blood The amount of oxygen bound to Hb depends on both **O₂ partial pressure** and **amount of Hb present**. Aortic blood S_aO2 ~ 98% Mixed venous blood S_aO2 ~ 75%

Answer 61

S-shaped curve provides key physiological advantages: * **_Plateau region_** ⇒ loading region * O₂ loaded onto Hb in pulmonary circulation * Allows saturation of Hb in the high partial pressure areas of the lung * Increasing P_O2 above 100 mmHg does not increase amount of O₂ bound to Hb * P_O2 down to ~60 mmHg before there is significant drop in Hb saturation * Safety net ensuring Hb saturation over wide range of P_aO2 * **_Steep region_** ⇒ unloading region * Large changes in oxygen saturation with small changes in P_O2 * Allows Hb to release large amounts of O₂ to tissues with small changes in P_O2 * **P₅₀** = P_aO2 where Hb is 50% saturated

Answer 62

Physiologically relavent effectors: **Decreases Hb oxygen affinity** Shifts dissociation curve to the **right** Greatest effect on the unloading or steep phase. **Facilitates release of O₂.** Assessed via P₅₀ → normal ~ 28 mmHg. * Increased levels of CO₂ * Increased temperature * Increased 2,3-BPG * Decreased pH * Decreased P_O2 due to tissue consumption \*Effects of CO₂ and pH termed Bohr effect.

Answer 63

**_Anemia_** * Decreased Hb content * Reduced O₂ content * Normal P_a_O2 * * Depends only on solubility of gas in plasma * Normal S_aO2 * oxygen content and max O₂ capacity reduced to similar degrees **_Polycythemia_** * Increased Hb content * Increased O₂ content * Unchanged S_aO2 and P_a_O2

Answer 64

**Reduces O₂ content without affecting S_aO2 or P_aO2.** * CO has much stronger affinity for Hb than O₂ * See reduction in O₂ content if 33% of sites bound with CO * Shifts dissociation curve **slightly left** * Makes it **harder to unload any O₂** bound to Hb

Answer 65

CO₂ transported in the blood in 3 forms: **_1. Dissolved in plasma (~10%)_** Governed by Henry's Law: [CO₂] = 0.67 x P_CO2 **_2. Bicarbonate (HCO₃ ~ 60%)_** CO₂ + H₂0 ↔︎ H₂CO₃ ↔︎ H⁺ + HCO₃^- Catalyzed by *carbonic anhydrase* in RBCs. H⁺ cannot exit & binds to Hb unloading O₂ ⇒ **Bohr effect**. HCO₃^- exchanged for Cl^- by *Cl/HCO₃^- exchanger* ⇒ **Chloride shift**. **_3. Carbamino Proteins (~30%)_** CO₂ + Hb-NH₂ ↔︎ Hb-NHCOOH CO₂ reacts with terminal amine groups on Hb producing **carbaminohemoglobin**. Hb can bind more CO₂ than it can bind O₂ to heme.

Answer 66

More or less linear over normal arterial CO₂ range. (35-50 mmHg) Higher [O₂] shifts curve downward ⇒ **Haldane effect**. Load more CO₂ at the tissues (low P_O2) Unload CO₂ at the lungs (high P_O2)

Answer 67

* Arterial content of CO₂ much greater than O₂. * Slope and linearity of CO₂ curve: * allows lungs to remove large amounts of CO₂ over extended range as P_CO2 increases

Answer 68

Role of pulmonary system in the regulation of pH. * HCO₃^- is the major physiological buffer * Ability of cells to maintain stable pH affected by: * alveolar ventilation rate * P_aCO2 * Decreased alveolar ventilation ⇒ increased P_aCO2 * Increased [H⁺]_plasma via carbonic anhydrase * Increased alveolar ventilation ⇒ decreased P_aCO2

Answer 69

* Buffers * **HCO₃^-** is the major physiological buffer * **Proteins** and **phosphates** act as _non-bicarbonate buffers_ * Calculate blood pH using the **Henderson-Hasselbach** equation * Since CO₂ obeys **Henry's Law**, equation can be modified as below. * Use **solubility constant of 0.03** due to conversion from mmHg to molar * Normal plasma [CO₂] = 40 mmHg and [HCO₃^-] = 24 mM * Normal plasma pH = 7.4

Answer 70

**Relationships between pH, P_CO2, and HCO₃^-.** We exist at the intersection of: **Buffer line** (BAC) **CO₂ isopleths** ⇒ represents constant P_CO2

Answer 71

**_Respiratory Disturbances_** When P_CO2 altered by _respiratory mechanisms_, the change in [HCO₃^-] will alter pH by traveling along the buffer line. **Compensation** via _renal regulation_ of: **HCO₃^- levels** **H⁺ production/excretion** Moves up or down to a new buffer line. * **Respiratory Acidosis (A ⇒ B)** * Decreased alveolar ventilation → increased P_CO2 * Kidney increases plasma [HCO₃^-] **(B ⇒ D)** * **Respiratory Alkalosis (A ⇒ C)** * Increased alveolar ventilation → decreased P_CO2 * Kidney reduces plasma [HCO₃^-] **(C ⇒ F)** **_Metabolic Disturbances_** Underlying cause due to alteration in plasma [HCO₃^-]. Alter P_CO2 via **respiratory compensation**. Moves to a new CO₂ isopleth.

Answer 72

Automatic process with a certain degree of voluntary control. Alter breathing rate and alveolar ventilation in response to blood chemistry. Functions through **feedback loops**: * **Central and peripheral sensors** * **Chemoreceptors** - detect blood gases * **Proprioceptors** - detect position * **Mechanoreceptors** - deter strest and irritants * Feed into the **respiratory center** - _central controller_ * Controls **muscles of respiration** - _effectors_

Answer 73

Breathing mainly regulated by _two centers_ with some degree of _cross-communication_ and _synchrony_: **_Dorsal Respiratory Group (DRG) ⇒ inspiratory center_** * Cell membrane potential with an **intrinsic oscillatory activity** * Increases in magnitude until threshold cross and action potential generated * AP → **Phrenic nerve** → Diaphragm and inspiratory muscles → initiate inspiration **_Ventral Respiratory Group (VRG) ⇒ expiratory center_** * **Quiescent during quiet breathing** * Tidal exhalation is a passive process * Role in forced expiration * Cells turn **off inspiration to start expiration** * Activate expiratory muscles to increase depth of expiration Output modulated by inputs from peripheral sources Breathing rate proportional to P_CO2 and inversely proportional to P_O2.

Answer 74

Involved in fine-tuning the medullary centers: **_Apneustic Center_** * In lower pons * **Excitatory effect** on the **inspiratory center** **_Pneumotaxic Center_** * In upper pons * **Switch off inspiration**

Answer 75

Alters the pulmonary system through conscious effort. Allows for fine control of breathing movements. Voluntary control eventually overidden by the central control systems in response to blood gas concentrations.

Answer 76

Sensitive to P_CO2 only through changes in pH. 60-80% of P_aCO2 effect on ventilation rate due to central chemoreceptors. 1. When P_CO2 rises, CO₂ diffuses across BBB into CSF and brain extracellular fluid (BECF) * BBB impermeable to HCO₃^- and H⁺ 2. H⁺ generated through formation of bicarbonate 3. H⁺ activates central chemoreceptors in medulla 4. Alters breathing rate via unknown mechanism * CSF and BECF with lower non-bicarb buffering capacity than plasma due to lower protein content * For given P_CO2 rise, change in [H⁺] greater in CSF than plasma * With prolonged respiratory acidosis, HCO₃^- levels increase * Blunts or eliminates the response to increases in P_CO2

Answer 77

**Sensitive to P_CO2, P_O2, and pH.** Located in **carotid** (more important) and **aortic bodies**. 20-40% of P_aCO2 effect on ventilation rate due to peripheral receptors. * Only **carotid receptors** respond to fall in **arterial pH** * Both respiratory and metabolic causes * H⁺ transported into cells where they stimulate the cell * Do not resond to changes in **P_O2 unti \< ~ 80 mmHg** (hypoxia) * Tracks **arterial blood O₂ saturation** * Mechanism likely involves inhibition of K⁺ channels leading to depolarization * Leads to neurotransmitter release to excite sensory afferents to CNS * O₂ and CO₂ chemoreceptors **interact** * Ex. drop in pH or P_O2 increases sensitivity of receptors to changes in P_CO2

Answer 78

Central and peripheral chemoreceptors vie for respiratory center control. Central receptors predominate until P_aO2 below 60 mmHg. Response to mild hypoxia over-diffen in favor of stable CO₂ concentration. * **_Increased P_CO2_** * **Peripheral receptors** act almost **immediately** * Leads to **rapid increase in ventilation rate** * **Central receptors** **slower** to respond * **Eventually predominate** to drive up ventilation rate * System **resets** to new higher P_CO2 with increased [HCO₃^-] in CSF * **_Decreased P_O2_** * Peripheral receptors not activated until very low P_O2 * Changers in P_O2 between 60-100 mmHg have little effect * **_Interactions between P_O2 and P_CO2_** * At given P_AO2, increases in P_ACO2 increase ventilation rate due to central and peripheral receptors. * **Hypoxia increases sensitivity of the response to P_ACO2** * Seen as changing slopes of curve in left panel * At given P_ACO2, decreasing P_O2 increases ventilation due to peripheral receptors * **Hypercapnea increases sensitivity of the response to hypoxia** * Seen as curves becoming steeper in the higher P_AO2 region of right panel

Answer 79

Cyclic breathing pattern (~30-100 secs): 1. Periods of apnea 2. Series of breaths of progressively increasing respiratory effort towards a maximum 3. Waning back to apnea Seen mostly in **heart failure** or at high altitudes. Low perfusion rates diminishes brainstem's ability to monitor effects of changing ventilation rates on gas composition in real time. * Time delay between central increase in ventilation rate and observation of changes in blood gas. * Overshoot in response reduces P_aCO2 below desired levels causing suppressed ventilation. * Same delay occurs with response to hypocapnia causing periods of apnea.

Answer 80

**Afferent fibers** located within **vagus nerve**. Three main groups of pulmonary receptors: 1. Pulmonary Stretch Receptors 2. Irritant Receptors 3. Juxtapulmonary Capillary REceptors (J-receptors)

Answer 81

**Slowly Adapting Pulmonary Stretch Receptors** **Hering-Breuer Reflex** * Located within **airway smooth muscle** * Discharge in reponse to **distention of the lung** * Activation triggers **excitation of the inspiratory OFF switch** * **Prolongs expiration** * Reflex inactive in humans unless **tidal volume \> 1 L** * Role in humans unclear

Answer 82

Rapidly Adapting Receptors * Located in **epithelium** of **larger conducting airways** * _Stimulated by:_ * noxious gases * cigarette smoke * inhaled dust * cold air * Inpulses travel up **vagus nerve** * Stimulation _results in_: * bronchoconstriction * mucous secretion * coughing * Relatively _inactive during normal breathing_ * Can be stimulated by lung inflation * **Responses wanes after a short period** * Implicated in bronchoconstriction triggered by histamine release with asthma attacks

Answer 83

* **Unmyelinated C fibers** located **within alveoli** * Similar characteristics and responses to irritant receptors * **Rapidly adapting** * Impulses travel via **vagus nerve** * _Can trigger_: * rapid shallow breathing * bronchoconstriction * mucous secretion

Answer 84

* **Joint, tendon, and muscle spindle receptors** * Located in **chest wall** * Sense **wall movement and effort** associated with breathing * Stimulation allows for **increased movement of chest wall** when movement impeded

Answer 85

* Proprioceptors located in limb joints * May trigger increased inhalation and exhalation during exercise

Pulmonary Flashcards

(112 cards)