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The RESPIRATORY SYSTEM

 Primary functions

 Major functional events

 Pulmonary ventilation

 Diffusion of O2 & CO2 between alveoli &

 Transport of O2 & CO2 in blood and body fluids

 Regulation of ventilation

2 Respiratory Gasses

 What essential function does O2 serve?

 How is CO2 produced and why do we need to get rid of it?

3 True or false: The you breathe in gets converted into that you then breathe out.

A) True B) False

4 Review of Respiratory Structures

 Upper vs. lower respiratory tracts

 Thoracic cavity

 Diaphragm

See Fig. 37-8

5 Review of Respiratory Structures

 Respiratory tree

 Trachea

 Bronchi

 Bronchioles

 Alveolar sacs

 Alveoli

6 See Fig. 37-8 Review of Respiratory Structures

 Structural characteristics

 Cartilage

 Cilia

glands

 Smooth muscle

See Fig. 37-8

7 Review of Respiratory Structures

 Respiratory membrane

 Blood-air barrier

 Epithelial characteristics

 Type I cells

 Type II cells

 Produce surfactant

8 See Fig. 37-8 Review of Respiratory Structures

 Pleurae (membranes)

 Parietal pleura

 Visceral pleura

 Pleural cavity

 Serous fluid

“float” in pleural cavities

9 Fluids in the respiratory system have all of these functions except…

A) Reducing friction of against chest wall B) Reducing surface tension in the lung C) Allowing gasses to diffuse across epithelium D) Transporting metabolic fuels to body tissues

10 Mechanics of

 Boyle’s Law

 P1V1 = P2V2

 The pressure of a gas varies inversely with its volume

  volume,  pressure =

  volume,  pressure =

 Air moves from area of high pressure to area of low pressure

11 Mechanics of Breathing

 Muscular events during inspiration

 Diaphragm contracts & flattens inferiorly

 External intercostals contract & elevate rib cage

  thoracic volume

Fig. 37-1 12 Mechanics of Breathing

 Muscular events during expiration

 Diaphragm relaxes & moves superiorly

 External intercostals relax, rib cage depressed

  thoracic volume

 Normal breath - recoil due to elasticity of lungs/thoracic cage

Fig. 37-1 13 Mechanics of Breathing

 Heavy breathing

 Inspiration

 Raise rib cage

 Exhalation

 Compress rib cage

Fig. 37-1 14 Mechanics of Breathing

 Thoracic pressures

 Intrapulmonary pressure (alveolar pressure)

 Pressure within alveoli

 Equalizes with atmospheric pressure

15 Mechanics of Breathing

 Thoracic pressures

 Intrapulmonary pressure (alveolar pressure)

 Pressure of fluid within pleural cavity

 < alveolar pressure

 Low pressure created by fluid draining into lymphatic capillaries

 Fluid/pressure causes visceral pleura to “stick” to parietal pleura

  as thoracic cavity expands, lungs expand

 Elasticity of lungs causes recoil, aids expiration

 Equalization with alveolar pressure = collapse 16 Mechanics of Breathing

 Thoracic pressures

 Intrapulmonary pressure (alveolar pressure)

 Intrapleural pressure

 Transpulmonary pressure

 Difference between intrapulmonary and intrapleural pressures

 Represents the elastic forces of the lungs

17 Thoracic Pressures

Fig. 37-1 18 Environmental pressure equalizes with which of the following pressures?

A) Transpulmonary pressure B) Pleural pressure C) Alveolar pressure D) All of the above

19

 Relationship of lung expansion and transpulmonary pressure

 Every 1 cm H2O increase in transpulmonary pressure results in 200 ml expansion in lung volume

 Characteristics determined by elastic forces of lungs

 Elasticity of lung tissue

 Surface tension within alveoli

20 Lung Compliance

 Tissue elasticity

 High percentage of elastic fibers in connective tissue of lungs

 Elastin & collagen

 Stretched during expansion then recoil

21 Lung Compliance

 Alveolar surface tension

 Alveolar surfaces covered with fluid

 Forms water-air surface

 Increases rate of gas diffusion

 Creates tension between water molecules

 Cohesive forces of water

 Surface tension

 Surfactants decrease surface tension

 Interfere with water cohesion

 Degree of recoil reduced

22 Lung Compliance

 Factors reducing lung compliance

 Reduced tissue elasticity

 Reduced surface tension

 Increased

 Mucus buildup

 Bronchial constriction

23 Lung compliance is affected by all of the following except…

A) Alveolar surface tension B) Elastic forces of lungs C) Airway resistance D) Size of alveoli

24 Pulmonary Volumes

(VT)

 Normal inspiration/expiration Fig. 37-6  ~ 0.5 L

 Inspiratory reserve volume (IRV)

 Air forceably inspired

beyond VT

 ~ 3 L

25 Pulmonary Volumes

 Expiratory reserve volume (ERV)

 Air forcibly expired beyond V T Fig. 37-6  ~ 1.1 L

 Residual volume (RV)

 Air that cannot be forcibly expired

 ~ 1.2 L

26 Pulmonary Capacities

 Inspiratory capacity (IC)

 Max. air inspired after normal expiration Fig. 37-6  TV + IRV

 ~ 3.5 L

 Functional residual capacity (FRC)

 Air remaining in lungs after normal expiration

 ERV + RV

 ~ 2.3 L

27 Pulmonary Capacities

(VC)

 Max. air inspired after normal expiration Fig. 37-6  IRV + TV + ERV

 ~ 4.6 L

 Total lung capacity (TLC)

 VC + RV

 ~ 5.8 L

28 Other Respiratory Measurements

 Minute respiratory volume

 Amount of air moved into respiratory passages each minute

 TV (ml) x (bpm)

 Air filling respiratory passages but not reaching areas

 ~ 0.15 L

29 The amount of air remaining in your lungs after a normal expiration is the…

A) Expiratory reserve volume B) Functional residual capacity C) Total lung capacity D) Residual volume

30 Determining Respiratory Volumes

 Functional residual capacity (He dilution method)

 Fill spirometer with known vol of air + known vol of He

 Expire normally then breathe from spirometer

 Air remaining in lungs = FRC Fig. 37-6

 [He] diluted by FRC gasses

 Calculate degree of dilution

31 Determining Respiratory Volumes

 Residual volume and total lung capacity

 Use FRC value

 RV = FRC - ERV

 TLC = FRC + IC or VC + RV Fig. 37-6

32 Determining Respiratory Volumes

 Dead space

 Breathe normally then take deep breath of pure O2

 Exhale into nitrogen meter

 First air expired = dead space  all O2

 [N2]  as alveolar air is expired

 [N2] plateaus as original alveolar concentration reached

 Area to left of curve = dead air space

33 Fig. 37-7 Alveolar Ventilation

 Rate at which “new” air reaches gas exchange area

 Good index of effective ventilation

 AVR (ml/min) = frequency x (VT - dead space)

 E.g., AVR = 12 b/min x (500 ml/b - 150 ml/b) = 4200 ml/min

 What this indicates…

 Slow/deep breaths   ventilation

 E.g., AVR = 10 b/min x (700 ml/b - 150 ml/b) = 5500 ml/min

 Rapid/shallow breaths   ventilation

 E.g., AVR = 15 b/min x (300 ml/b - 150 ml/b) = 2250 ml/min

34 If you want to increase the amount of new air in the lungs, you should…

A) Breathe more quickly B) Breathe more deeply

35 Gas Exchange Across Respiratory Membranes

 Dalton’s Law of Partial Pressures

 Total gas pressure = sum of partial pressures of gasses within the mixture

36 Gas Exchange Across Respiratory Membranes

Partial pressure of atmospheric gasses (sea level) mmHg %

N2 597.0 78.62

O2 159.0 20.84

CO2 0.3 0.04

H2O 3.7 0.50 Total 760.0 100.00

See Table 39-1 37 Gas Exchange Across Respiratory Membranes

 Henry’s Law

 When a gas mixture is in contact with a liquid, each gas will dissolve in proportion to its partial pressure and relative to its solubility in the liquid

conc. of dissolved gas partial pressure = solubility coefficient

   solubility, more gas can dissolve without building up excess partial pressure

38 Gas Exchange Across Respiratory Membranes

Solubility coefficients of important respiratory gasses

PO2 0.024

PCO2 0.570 PCO 0.018

PN2 0.012 PHe 0.008

39 Gas Exchange Across Respiratory Membranes

 Diffusion coefficient

 Relative rates at which different gasses at same pressure levels will diffuse

 Depends on molecular weight of the gas & solubility

O2 1.0

CO2 20.3 CO 0.81

N2 0.53 He 0.95

40 Gas Exchange Across Respiratory Membranes

 Volume of gas that will diffuse through the membrane each minute at a partial pressure difference of 1 mmHg

41 Diffusing Capacity

 O2 (at rest)

 ~ 21 ml/min/mmHg

 Pressure difference across membrane ~ 11 mmHg

  O2 diffusion = 11 x 21 = 230 ml/min (same as use rate)

42 Fig. 39-10 Diffusing Capacity

 O2 (during exercise)

 ~ 65 ml/min/mmHg (max)

 ~ 3x increase due to…

 Increased (dilation)

 Increases diffusing capacity

 Increased ventilation- ratio

43 Fig. 39-10 Diffusing Capacity

 CO2

 ~ 400-450 ml/min/mmHg (at rest)

 Theoretical

 ~20x O2

 Pressure difference across membrane > 1 mmHg

 Less pressure difference but higher solubility & diffusion coefficients

Fig. 39-10 44 The diffusing capacity of a membrane for a particular gas depends on all of these except:

A) diffusion coefficient of the gas B) pressure difference of the gas across membrane C) thickness of membrane D) absolute concentration of the gas in the blood

45 Alveolar Air

 Composition differs from atmosphere

 Humidified

 Continual diffusion of CO2 into alveoli

 Continual diffusion of O2 into blood

See Table 39-1 46 Alveolar Air

 Only partially replaced

 FRC ~2.3 L, only ~350 ml “fresh” air enters alveoli

 Takes multiple breaths (16+) to completely replace

 Slow replacement important to prevent sudden changes in gas concentration in the blood

Fig. 39-2 47 Alveolar air is replaced slowly, over the course of ~16 breaths, because…

A) the volume of air breathed in is small in relation to dead space B) the volume of air breathed in is small in relation to the functional reserve capacity C) the old air prevents new air from coming into the lung well D) the speed of air intake is insufficient to push old air out

48 Factors Influencing Rate of Diffusion Through Membrane

 Membrane thickness

 Averages ~0.6 m

  thickness (i.e., edema),  diffusion

Fig. 39-8 Fig. 39-9 49 Factors Influencing Rate of Diffusion Through Membrane

 Membrane thickness

 Averages ~0.6 m

  thickness (i.e., edema),  diffusion

 Surface area 2  ~60-70 m

 Partial pressure gradients

 Gas solubilities

50 Diffusion of O2 & CO2 Across the Respiratory & Cellular Membranes

O2 CO2

Fig. 40-1 & 3 Fig. 40-6 & 5 51 Systemic PO2

Fig. 40-2

52 Carbon dioxide moves from alveolar capillaries into alveoli because…

A) Concentration of oxygen is higher in alveoli than in the blood B) Partial pressure of carbon dioxide is higher in alveoli than in the blood C) Concentration of carbon dioxide is higher in blood than in alveoli D) Partial pressure of carbon dioxide is higher in blood than in alveoli

53 Ventilation-Perfusion Coupling

 Synchronization of blood flow with gas concentrations

 Function

 Redirect blood to where it is most needed for gas exchange

54 Ventilation-Perfusion Coupling

 Alveolar capillaries

 Respond to PO2

 PO2  arterioles around  reduced perfusion (inadequate alveoli constrict (blood flow) ventilation)

Less O2  reduce blood flow around affected alveoli

 PO2  arterioles around  increased perfusion (adequate alveoli dilate (blood flow) ventilation)

More O2  increase blood flow around affected alveoli

55 Ventilation-Perfusion Coupling

 Bronchioles

 Respond to PCO2

Alveoli Bronchioles

 PCO2 Dilate (increase expiration volume)

 PCO2 Constrict

56 Ventilation-Perfusion Ratio

 Reflects respiratory exchange when alveolar

ventilation (VA) and blood flow (Q) are imbalanced

 V-P ratio = VA/Q

 VA = alveolar ventilation, Q = blood flow   ratio compared to normal

 Adequate blood flow but poor ventilation

 Alveolus [O2/CO2] equilibrates with pulmonary capillary blood  Blood shunted away from affected capillaries (physiologic shunt)

 Reduced oxygenation of pulmonary venous blood 57 Ventilation-Perfusion Ratio

 Reflects respiratory exchange when alveolar

ventilation (VA) and blood flow (Q) are imbalanced

  ratio compared to normal

 Adequate ventilation but poor blood flow

 Alveolus [O2/CO2] equilibrates with inspired air

 Physiologic dead space (wasted ventilation)

58 Ventilation-perfusion coupling imbalances may result in…

A) Increased physiological dead space B) Wasting of energy due to unnecessary ventilation C) Poor oxygenation of blood D) All of the above

59 Transport of O2 in Blood

 Bound to

 ~97%

 Dissolved in plasma

 ~3%

60 Hemoglobin (Hgb)

 Hemoglobin

 Tetramer

 Globin polypeptides

  &  chains most common

 1 / chain

 Heme group

 Porphyrin ring with Fe See Fig. 32-6 core

 Pigment

61 Hemoglobin (Hgb)

 O2 binding

 1 O2 / heme group

 4 heme groups / Hgb ( 4 O2 / Hgb)

62 Hemoglobin (Hgb)

 O2 binding & pigment development

 Causes conformational change in heme group

 Oxyhemoglobin (HgbO2) = bright red

 Deoxyhemoglobin (HHgb) = dark red

lungs + HHgb + O2  HgbO2 + H tissues

63 Hemoglobin (Hgb)

 O2 binding & Hgb saturation st  1 O2 binds

 Partial saturation

 Conformational change increases uptake of

additional O2

 Remaining 3 O2 bind

 Full saturation

64 Oxygen binds to…

A) The alpha chain of hemoglobin B) The beta chain of hemoglobin C) The heme portion of hemoglobin D) All of the above

65 O2/Hgb Dissociation Curve

 Reflects affinity of O2 for Hgb at different PO2

 Observations to note

 At PO2 of 40 (venous blood), Hgb is still ~70% saturated

 Venous reserve

Fig. 40-8 66 O2/Hgb Dissociation Curve

 Reflects affinity of O2 for Hgb at different PO2

 Observations to note

 Decreased alveolar PO2 can still allow adequate O2 binding ( elevation)

Fig. 40-8 67 O2/Hgb Dissociation Curve

 Changes in metabolic factors can shift curve

& affect O2 loading/unloading

 Shift to right → increase O2 unloading

 Shift curve to left → increase O2 loading

loading

unloading

Fig. 40-8 68 Factors Influencing O2/Hgb Dissociation Curve

 Any increase in the following factors shifts the curve to the right

 Temperature +  H

 PCO2

 BPG (2,3-bisphosphoglycerate)

 Method

  O2 affinity for Hgb

  dissociation (unloading)

Fig. 40-10

69 Oxygen can be offloaded more easily when…

A) Carbon dioxide partial pressure is increased B) Blood is more alkaline C) Body temperature falls D) All of the above

70 Transport of CO2 in Blood

 Dissolved in plasma

 ~7-10%

 Bound to Hgb

 ~20-30%

(HgbCO2)

 Binds to globin  doesn’t compete with O2 binding sites on heme

 Binds most rapidly to HHgb than HgbO2

71 Transport of CO2 in Blood

 Dissolved in plasma

 ~7-10%

 Bound to Hgb

 ~20-30%

 As ions in plasma

 ~60-70%

- + CO2 + H2O  H2CO3  HCO3 + H bicarbonate

72 Bicarbonate Buffering System

+  Dissociation of carbonic acid (H )

 RBC +  H + Hgb  HHgb

 Buffering

 Weakens HgbO2  enhances O2 unloading

See Fig. 40-13 73 Bicarbonate Buffering System

-  Dissociation of carbonic acid (HCO3 )  -  Diffusion of HCO3 from RBC to plasma -  Countered by influx of Cl from plasma into RBC  Maintains charge balance  Gradient favors anabolic action of carbonic anhydrase

See Fig. 40-13 74 Bicarbonate Buffering System

 CO2 transport to lungs

  PCO2 in blood

See Fig. 40-13 75 True or false: Carbonic anhydrase may catalyze opposite reactions depending on conditions.

A) True B) False

76 Bohr Effect

 Effect of changes in pH and CO2 on the unloading / loading of O2 with hemoglobin  Tissues

 Uptake of CO2… +   carbonic acid ( H )

 O2-Hb curve shifts right   O2 affinity for Hgb ( O2 unloading)

77 Bohr Effect

 Effect of changes in pH and CO2 on the unloading / loading of O2 with hemoglobin  Lungs

 Removal of CO2… +   carbonic acid ( H )

 O2-Hb curve shifts left   O2 affinity for Hgb ( O2 loading)

78

 Effect of O2/Hgb binding on the displacement & uptake of CO2

 Lungs +  HgbO2 formation (O2 loading) releases H

  tendency of Hgb to form HgbCO2

 Drives catabolic action of carbonic anhydrase (CO2 formation)

79 Haldane Effect

 Effect of O2/Hgb binding in the displacement & uptake of CO2

 Tissues

 HgbO2 dissociation (O2 unloading) frees Hgb

 Favors HHgb & HgbCO2 formation +  H utilization drives anabolic action of carbonic anhydrase

80 The ability of protons to influence O2 loading to hemoglobin is the…

A) Haldane effect B) Bohr effect

81 Regulation of

 Respiratory centers in & pons

 Dorsal respiratory group (DRG)

 Inspiratory center (sets respiratory rhythm)

 Sensory input from vagus & glossopharyngeal nerves Fig. 41-1 

 Baroreceptors

 Sensory receptors within lungs

82 Regulation of Respiration

 Respiratory centers in medulla oblongata & pons

 Dorsal respiratory group (DRG)

 Output to primary respiratory muscles (phrenic nerve)

 “Ramp signal”

 Gradually increases contraction

 Steady increase in lung volume

 Abrupt stop (expiration); recoil

83 Regulation of Respiration

 Respiratory centers in medulla oblongata & pons

 Ventral respiratory group (VRG)

 Inspiration & expiration

 Respiratory “overdrive”

 Inactive during normal respiration

 Activated with forced/increased breathing

 Stimulate muscular activity of both inspiration & expiration 84 Regulation of Respiration

 Respiratory centers in medulla oblongata & pons

 Pneumotaxic center

 Controls rate & pattern of breathing by limiting duration of inspiration

 Controls DRG ramp “switch-off” point

 Strong  signal shortens ramp-up time

  inspiration rate (30-40 bpm)

  inspiration depth

85 Regulation of Respiration

 Respiratory centers in medulla oblongata & pons

 Pneumotaxic center

 Controls rate & pattern of breathing by limiting duration of inspiration

 Controls DRG ramp “switch-off” point

 Strong  signal lengthens ramp-up time

  inspiration rate (3-5 bpm)

  inspiration depth

86 Hering-Breuer Inflation Reflex

 Response of lung inflation to limit respiration

 Functions to protect against excess stretch

 Inflation of lungs increases output signal from baroreceptors

 Increased stimulus (vagal afferents) inhibits DRG

 Terminates inspiration (ramp-off)

 Sensory receptors within lungs

 Deflation of lungs decreases output signal from baroreceptors

 Decreased stimulus (vagal afferents), DRG not inhibited

 Begins ramp-up 87 Which center in the medulla is primarily responsible for setting respiratory rate?

A) Dorsal respiratory group B) Pneumotaxic center C) Ventral respiratory group D) All of the above

88 Chemical Control of Respiration

 Goal of respiration +  Maintain O2, CO2, H concentrations in blood & tissues

 Control of respiration +  Response to changes in O2, CO2, H concentrations +  CO2 & H act centrally on respiratory centers

 O2 input from peripheral locations

89 CO2, Blood pH and Regulation of Breathing

Fig. 41-3 90 + CO2, H & Respiratory Control

 Chemosensitive area of

  blood [CO2] provides indirect stimulation

 CO2 diffuses into chemosensitive area

 Reacts with H2O in tissues +   blood PCO2   tissue PCO2   H

 Effect

  ventilation

91 Fig. 41-2 CO2, Blood pH and Regulation of Breathing

 Carbonic acid-bicarbonate buffering system

- + CO2 + H2O  H2CO3  HCO3 + H

  pH drives equilibrium +   pH ( H )  Drives equation left  Rapid / deep breathing

 Releases more CO2  raises pH (removes free H+) +   pH ( H )  Drives equation right  Slow / shallow breathing

 Retains more CO2  lowers pH (increases free H+) 92

O2 & Respiratory Control

 Peripheral chemoreceptors

 Stimulated by  arterial PO2 +  Lesser extent by CO2 & H

 Primarily carotid & aortic bodies

 Carotid bodies

 Afferents (Hering’s  glossopharyngeal)

 Synapse at DRG

 Aortic bodies

 Afferents (vagus)

 Synapse at DRG

93 Fig. 41-4

O2 & Respiratory Control

 Effect of  arterial PO2

 As PO2 decreases (< 100 mmHg)…

 Impulse rate to respiratory centers increases

  ventilation

Fig. 41-5 Fig. 41-6 94 True or false: Oxygen drives breathing rate more than carbon dioxide.

A) True B) False

95 Respiratory Insufficiency

 Inadequate delivery of O2 to tissues

 Cyanosis

 Skin, mucosa, nail beds turn “blue”

 Depressed mental activity (may lead to coma)

 Reduced muscle activity

 Cell death

96 Respiratory Insufficiency

 Asthma

 Hypersensitivity (allergy) to airborne substances

 Reaction

 Immune response

 Release of leukotrienes, bradykinin, histamine, etc.

 Localized edema (walls of bronchioles)

 Smooth muscle spasm (bronchioles)

 Increased airway resistance (decreased ventilation)

 Expiration difficulty

 May cause dyspnea 97 Respiratory Insufficiency

 Asthma

 Common treatments

 Simulate sympathetic response (bronchiole dilation)

 Immediate relief

 Corticosteroid aerosols

 Long term therapy

 Reduce frequency / intensity of attacks

98 Respiratory Insufficiency

 Effect of CO

 Competes with O2 for heme sites on Hb

 ~250x affinity for Hb

 At PCO of 0.4 mmHg in alveoli, competes equally with O2 for Hb

 Treatment

  PO2 (pure O2)

 Greater pressure differential displaces CO

  PCO2

 Increase ventilation

99 True or false: Oxygen drives breathing rate more than carbon dioxide.

A) True B) False

100