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1 Respiratory System

1 Respiratory System

For the body to survive, there must be a constant supply of

O2 and a constant disposal of CO2

Respiratory System

Respiratory System - Overview:

Assists in the detection Protects system of odorants (debris / pathogens / dessication)

5 3

4 Produces sound (vocalization) Provides surface area for (between air / )

1

2

Moves air to / from gas exchange surface

Marieb & Hoehn ( and Physiology, 8th ed.) – Table 19.1

1 Respiratory System

Functional Anatomy:

Epiglottis

Upper Respiratory • Conduction of air System • Gas exchange

• Filters / warms / humidifies Lower Respiratory incoming air System

1) External nares 5) 2) • Provide open airway • Resonance chamber • channel air / food 3) Uvula • voice production (link) 4) 6) • Nasopharynx 7) Bronchial tree 8) Alveoli • Oropharynx • Laryngopharynx

Martini et. al. (Fundamentals of Anatomy and Physiology, 7th ed.) – Figure 23.1

Respiratory System

Functional Anatomy:

Trachea

Naming of pathways: • > 1 mm diameter = • < 1 mm diameter = bronchiole Primary • < 0.5 mm diameter = terminal bronchiole Bronchus Bronchi bifurcation (23 orders)

Green = Conducting zone Purple = Respiratory zone

Bronchiole Terminal Bronchiole Respiratory Bronchiole Alveolus

Martini et. al. (Fundamentals of Anatomy and Physiology, 7th ed.) – Figure 23.9

2 Respiratory System

Functional Anatomy: Respiratory Mucosa / Submucosa:

Near Near trachea alveoli

Epithelium: Pseudostratified Simple columnar cuboidal

Cilia No cilia

Mucosa: Lamina Propria (areolar layer): Mucous membrane ( / areolar tissue)  smooth  muscle

Mucous No glands mucous glands :

Rings Plates / none

Martini et. al. (Fundamentals of Anatomy and Physiology, 7th ed.) – Figure 23.9

Respiratory System

Functional Anatomy:

How are inhaled debris / pathogens cleared from ?

Nasal Cavity: Particles > 10 µm

Conducting Zone: Particles 5 – 10 µm

Respiratory Zone: Escalator Particles 1 – 5 µm

Macrophages Martini et. al. (Fundamentals of Anatomy and Physiology, 7th ed.) – Figure 23.2

3 Respiratory System

Functional Anatomy: Pseudostratified ciliated columnar epithelium

Trachea

Goblet cells: Unicellular mucous secreting glands

Esophagus

Tough, flexible tube 15 – 20 tracheal (~ 1” diameter) (C-shaped) • Protect airway • Allow for food passage

Martini et. al. (Fundamentals of Anatomy and Physiology, 7th ed.) – Figure 23.9

Respiratory System

Functional Anatomy:

Right primary bronchus wider, shorter & steeper ( blockage )

Bronchus (> 1 mm diameter) • 1º = Extrapulmonary bronchi • 2º  = Intrapulmonary bronchi

Bronchitis: Inflammation of airways Pseudostratified ciliated columnar epithelium

Smooth muscle

Cartilage plate

Martini et. al. (Fundamentals of Anatomy and Physiology, 7th ed.) – Figure 23.9

4 Respiratory System

Functional Anatomy: Mucous glands rare – Why? Pseudostratified ciliated columnar epithelium

Cartilage plates?

Thick smooth muscle

Allergic attack =  Histamine =

Sympathetic stimulation (NE; 2 receptors) • Leads to bronchodilation

Synthetic drugs (e.g., albuterol) E (medulla) triggers Bronchiole trigger response response (< 1 mm diameter) Parasympathetic stimulation (ACh; muscarinic receptors) • Leads to bronchoconstriction Alveoli (300 million / ) Martini et. al. (Fundamentals of Anatomy and Physiology, 7th ed.) – Figure 23.9

Respiratory System

Functional Anatomy: Surrounded by fine elastic fibers Respiratory bronchiole

Terminal Alveolar bronchiole sac

Type I Pneumocytes: • Simple squamous; forms wall of alveoli Total surface area: • Alveolar pores (1 – 6 / alveoli) 75 - 90 m2 (~1/2 tennis court) Type II Pneumocytes:

200 m • Cuboidal / round; secrete • Reduces (stops alveoli collapse)

Alveolar macrophages: • Clear debris on alveolar surface

Alveolar pores Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.8

5 Respiratory System : Functional Anatomy: Thickening of respiratory membrane

Gas exchange occurs readily in the alveoli of the lung via simple across the respiratory membrane

0.1 – 0.5 m thick

Respiratory Membrane: 1) Type I pneumocytes 2) Endothelial cells of 3) Fused basement membranes

Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.9

Respiratory System

Respiratory Physiology:

Respiration includes: 1 1) Pulmonary ventilation (pumping air in / out of )

2) External (gas exchange @ blood-gas barrier) 2 3) Transport of respiratory gases (blood)

4) Internal respiration (gas exchange @ tissues)

3

4

Randall et al. (Eckert Physiology, 5th ed.) – Figure 13.19

6 Respiratory System

Pulmonary Ventilation: Simplified Model:

Trachea Trachea Visceral pleura Lung

Parietal Pleural pleura cavity

Thoracic wall

Lung

Pleural cavity Diaphragm wall

Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.12

Respiratory System

Pulmonary Ventilation:

Atmospheric = ~ 760 mm Hg

(Consider Patmospheric = 0 mm Hg)

Pressure relationships in the :

1) Intrapulmonary Pressure (w/in the alveoli): • Static conditions = 0 mm Hg

• (inspiration) = Ppul slightly negative

Intrapulmonary • (expiration) = Ppul slightly positive pressure (P = 0 mm Hg) pul 2) Intrapleural pressure (w/in ): • Always relatively negative (~ - 4 mm Hg) • Prevents lungs from collapsing

Diaphragm Intrapleural pressure (Pip = - 4 mm Hg)

= Patm = 0 mm Hg

7 Respiratory System

Pulmonary Ventilation:

Why is the intrapleural pressure negative?

Answer: Interaction of opposing

Forces equilibrate at Pip = - 4 mm Hg Forces acting to collapse lung:

1) Elasticity of lungs Surface tension of 2) Alveolar surface tension serous fluids keep lungs “stuck” to resisting lung collapse: chest wall 1) Elasticity of chest wall

Pneumothorax: (“sucking chest wound”) Puncture of chest wall; results in inability to generate negative pressure and expand the lungs Costanzo (Physiology, 4th ed.) – Figure 5.9

Respiratory System

Pulmonary Ventilation:

Pulmonary ventilation is a mechanical process that depends on thoracic cavity volume changes

Boyle’s Law:

P1V1 = P2V2

P = pressure of gas (mm Hg) V = volume of gas (mm3)

P1 = initial pressure; V1 = initial volume

P2 = resulting pressure; V2 = resulting volume

3 3 Example: 4 mm Hg (2 mm ) = P2 (4 mm ) P2 = 2 mm Hg

CHANGING THE VOLUME RESULTS IN INVERSE CHANGE OF PRESSURE

Martini et. al. (Fundamentals of Anatomy and Physiology, 7th ed.) – Figure 23.13

8 Respiratory System

Pulmonary Ventilation:

Pulmonary ventilation is a mechanical process that depends on thoracic cavity volume changes

0 mm Hg Inspiration: Muscular expansion of thoracic cavity - 4 mm Hg A) Contraction of diaphragm • Lengthens (pushes down) B) Contraction of external • Widens thorax 0 mm Hg

Diaphragm

Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.13

Respiratory System

Pulmonary Ventilation:

Pulmonary ventilation is a mechanical process that depends on thoracic cavity volume changes

0 mm Hg Inspiration: Muscular expansion of thoracic cavity - 6 mm Hg A) Contraction of diaphragm • Lengthens thorax (pushes liver down) B) Contraction of external intercostal muscles • Widens thorax - 1 mm Hg Results in:

• Reduced intrapleural pressure (Pip)

• Reduced intrapulmonary pressure (Ppul)

Results in decreased pressure in thoracic cavity and air enters Diaphragm

9 Respiratory System Internal pressure Pulmonary Ventilation: can reach +100 mm Hg (e.g., why you should exhale when lifting )

Pulmonary ventilation is a mechanical process that depends on thoracic cavity volume changes

Results in increased pressure 0 mm Hg Expiration: in thoracic cavity; air exits Retraction of thoracic cavity - 4 mm Hg A) Passive Expiration • Diaphragm / external intercostals relax • Elastic rebound (lungs rebound)

B) Active (“Forced”) Expiration +10 mm Hg • Abdominal muscles contract • Internal intercostals contract

Eupnea: : Quiet Forced breathing Diaphragm (active inspiration; (active inspiration; (passive expiration) (active expiration)

Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.13

Respiratory System

Pulmonary Ventilation:

Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.14

10 Respiratory System

Pulmonary Ventilation:

Several physical factors exist influence pulmonary ventilation

A)

Q = Airflow (L / min) Q = P / R P = Pressure gradient (mm Hg) R = Airway resistance (mm Hg / L / sec)

Airflow is directly proportional to pressure difference between outside air and alveoli and inversely proportional to resistance of the airway

Resistance determined by Why don’t the smallest airways provide the highest resistance? Poiseuille’s Law: Medium-sized bronchi 8Lη Reminder: R = Parasympathetic system produces 4 r bronchial constriction Terminal ( diameter =  resistance) R = Resistance

η = Viscosity of inspired air Resistance Sympathetic system produces L = Length of airway bronchial dilation ( diameter =  resistance) r = of airway Bifurcation stage

Respiratory System

Respiratory Distress Syndrome Pulmonary Ventilation: (e.g., pre-mature babies)

Several physical factors exist influence pulmonary ventilation

B) Surface tension in alveoli

Surface tension generated as neighboring liquid molecules on the surface of alveoli are drawn together by attractive forces Pressure required to keep alveolus open

P = Collapsing pressure on alveolus (dynes / cm2) 2T T = Surface tension (dynes / cm) Law of Laplace: P = r r = Radius of alveolus (cm)

Surfactant

Problem?

Dipalmitoyl phosphatidylchorine (DPPC) Costanzo (Physiology, 4th ed.) – Figure 5.12

11 Respiratory System

Pulmonary Ventilation:

Several physical factors exist influence pulmonary ventilation

C)

Measure of change in lung volume that occurs with a given transpulmonary pressure

C = Lung compliance (cm3 / mm Hg) V L L V = Lung volume (cm3) C = L L P = Intrapulmonary pressure (mm Hg)  (P – P ) pul pul ip Ppi = Intrapleural pressure (mm Hg) (Transmural pressure)

Barrel Chest The higher the lung compliance, the easier Emphysema: it is to expand the lungs at a given pressure Increased lung compliance due to loss of elastic fibers Determined by: 1) Elasticity of lung : 2) Surface tension Decreased lung compliance due to scar tissue build-up

Respiratory System : Pulmonary Ventilation: Amount of air moved into / out of lung during single respiratory cycle

Respiratory Volumes / Capacities:

(spirometric reading)

Increases with: • Body size Inspiratory reserve • Gender Volume (IRV) Inspiratory • Conditioning (~ 3100 ml) capacity (~ 3600 ml) (~ 4800 ml)

Decreases with: Resting Tidal Volume (~ 500 ml) • Age Expiratory reserve volume (~ 1200 ml) Functional residual capacity Total lung Residual volume (~ 1200 ml) (~ 2400 ml) capacity (~ 6000 ml) (Male)

(Female ~ 4200 ml) Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.16

12 Cardiovascular System – Vessels

Pathophysiology:

Forced vital capacity (FVC) is the total volume of air that can be forcibly expired after maximal inspiration; this is a useful measure of lung disease

FEV = Forcefully expired volume

FEV1 FVC < 0.8 > 0.8 • Both FEV and FVC low but • Both FEV and FVC low but 0.8 1 1 FEV1 decreased more than FVC decreased more than FVC FEV1

Costanzo (Physiology, 4th ed.) – Figure 5.6

Respiratory System Physiologic : Anatomic dead space plus any Pulmonary Ventilation: ventilated alveoli that might not participate in gas exchange Not all inhaled air participates in gas exchange; this volume is referred to as dead space

Anatomic Dead Space: Rule of Thumb: Volume of air found in the Anatomical dead space in a healthy conducting airways, including young adult is equal to 1 ml / pound of ideal body the  bronchioles

Costanzo (Physiology, 4th ed.) – Figure 5.3

13 Respiratory System

Pulmonary Ventilation:

Ventilation rate is the volume of air moved into an out of the lungs per unit time

Minute Volume:

VM = f (breaths / minute) x VT (tidal volume) = 12 breaths / minute x 500 mL

= 6000 mL / minute

= 6.0 liters / minute

Alveolar Ventilation: (or physiologic dead space)

VA = f (breaths / minute) x (VT (tidal volume) - VD (anatomic dead space)) = 12 breaths / minute x (500 mL - 150 mL)

= 4200 mL / minute Available for gas transfer… = 4.2 liters / minute

Respiratory System

Respiratory Physiology:

Respiration includes: 1 1) Pulmonary ventilation (pumping air in / out of lungs)

2) External respiration (gas exchange @ blood-gas barrier) 2 3) Transport of respiratory gases (blood)

4) Internal respiration (gas exchange @ tissues)

3

4

Randall et al. (Eckert Animal Physiology, 5th ed.) – Figure 13.19

14 Respiratory System

Pulmonary Ventilation:

Gas exchange in the respiratory system refers to diffusion of

O2 and CO2 in the lung and in the peripheral tissues

Basic Properties of Gases:

A) Dalton’s Law of Partial :

The total pressure of a gas is equal to the sum of the pressure of its constituents

Patmosphere: For dry gases: 21% 760 mm Hg P = P x F O2 X B

PX = of gas (mm Hg)

PB = Barometric pressure (mm Hg) F = Fractional of gas 79% N 2 P = 760 x 0.21 O2 P = 160 mm Hg O2 % Composition of Atmospheric Air

Respiratory System

Gas Exchange:

Gas exchange in the respiratory system refers to diffusion of

O2 and CO2 in the lung and in the peripheral tissues

Basic Properties of Gases:

A) Dalton’s Law of Partial Pressures:

The total pressure of a gas is equal to the sum of the pressure of its constituents

Patmosphere: For humidified gases: 21% 760 mm Hg P = (P – P ) x F O2 X B H2O

PX = Partial pressure of gas (mm Hg)

PB = Barometric pressure (mm Hg) P = Water vapor pressure at 37C (47 mm Hg) H2O 79% F = Fractional concentration of gas N 2 P = (760 – 47) x 0.21 O2

PO = 150 mm Hg % Composition of Atmospheric Air 2

15 Respiratory System Note: At equilibrium, the partial pressure Gas Exchange: of a gas in the liquid phase equals the partial pressure in the gas phase

Gas exchange in the respiratory system refers to diffusion of

(the “bends”) O2 and CO2 in the lung and in the peripheral tissues

CO >> O >> N Basic Properties of Gases: 2 2 2 : How much of a gas will dissolve in a B) Henry’s Law: liquid at a given partial pressure Gases in a mixture dissolve in a liquid in proportion to their partial pressures

CX = PX x Solubility

CX = Concentration of dissolved gas (mL X / 100 mL blood)

PX = Partial pressure of gas (mm Hg) Solubility = Solubility of gas in blood (mL X / 100 mL / mm Hg)

[O ] = P x Solubility 2 O2

[O2] = 150 x 0.003

[O2] = 0.45 mL / 100 mL blood

Respiratory System

Gas Exchange:

Gas exchange in the respiratory system refers to diffusion of O and CO in the lung and in the peripheral tissues Respiratory 2 2 membrane

Basic Properties of Gases:

C) Fick’s Law:

The transfer of a gas across a cell membrane depends on the driving force, gas solubility, and the surface area available for transport

DAP directly proportional VX = The driving force for diffusion of a gas is the x inversely proportional partial pressure difference of the gas, not the concentration difference

VX = Volume of gas transferred per unit time 60 D = Diffusion coefficient of the gas (includes solubility) P P O2 O2 A = Surface area in lung 100 40 in blood P = Partial pressure difference of the gas X = Thickness of the membrane

16 Respiratory System In , only dissolved gases Gas Exchange: contribute to partial pressures

Unlike alveolar air, where there is only one form of gas, blood is able to carry gases in addition forms

PX

Bound gas Dissolved gas Chemically modified gas Gases bind directly The higher the solubility to plasma proteins or of a gas, the higher the Gases react with blood to concentration of the gas components to form in solution new products

Total gas concentration = Dissolved gas + Bound gas + Chemically modified gas

Respiratory System

Gas Exchange:

Gas transport in the lungs:

Costanzo (Physiology, 4th ed.) – Figure 5.16

17 Costanzo (Physiology, 4th ed.) – Figure 5.17 Respiratory System

Gas Exchange: Systemic tissues undergo reversal of pattern observed at lung Patmosphere: 760 mm Hg DAP Gas transport in the lungs: VX = x O2 = 21% PX = PB x F CO2 = 0% Diffusional coefficient 20x greater

for CO2 than for O2

O2 = 21% CO2 = 0% Lung air modified by gas exchange: P = (P – P ) x F X B H2O 1) O2 into blood; CO2 out of blood 2) Mixture of fresh and residual air O2 = 14% CO2 = 6% P = 60 O2 P = (P – P ) x F X B H2O P = 6 CO2

The amount of O2 / CO2 transferred corresponds to the needs of the body Composition reflects 1:1 exchange rate Due to rapid diffusion metabolic activity of body of gases, equilibrium reached ?

Costanzo (Physiology, 4th ed.) – Figure 5.18 Respiratory System

Gas Exchange:

Gas exchange across the alveolar / pulmonary barrier is described as either diffusion-limited or -limited

Diffusion-limited: Perfusion-limited: The total amount of gas transported The total amount of gas transported across the alveolar / capillary barrier is across the alveolar / capillary barrier is limited by the diffusional process limited by blood flow

Partial pressure gradient maintained across entire length of capillary Example: Example: Carbon Nitrous (gas does not equilibrate) Partial pressure monoxide oxide gradient not maintained across length of capillary (gas equilibrates)

 gas transport =  diffusion rate  gas transport =  blood flow

18 Respiratory System

Gas Exchange:

Under normal conditions, O2 transport into pulmonary capillaries is a perfusion-limited process

Exercise Rest

“wiggle room”

PO does not equilibrate until

(mmHg) 2

2 hemoglobin saturated

O P Remember: P only measures free O2 O2 concentration

Time in pulmonary capillary (s)

Start of End of capillary capillary

Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.18

Respiratory System

Pathophysiology:

In certain pathologic conditions, O2 transport becomes diffusion limited Lung fibrosis

P equilibrium never O2 reached

Outcome:

Decreased PO2 in systemic Alveolar wall thickens; slows , especially down diffusion rate during physical activity

DAP V = X x

Costanzo (Physiology, 4th ed.) – Figure 5.19

19 Respiratory System

A man climbs to the top of a tall mountain where the barometric pressure is measured at 50 mm Hg.

What are the implications to transport into pulmonary capillaries for A) Pa , O2 B) rate, and C)

Exercise Rest Driving force: 50 – 25 = 25 mm Hg

DAP “shortness VX = of breath” x

Costanzo (Physiology, 4th ed.) – Figure 5.19

Respiratory System

Respiratory Physiology:

Respiration includes: 1 1) Pulmonary ventilation (pumping air in / out of lungs)

2) External respiration (gas exchange @ blood-gas barrier) 2 3) Transport of respiratory gases (blood)

4) Internal respiration (gas exchange @ tissues)

3

4

Randall et al. (Eckert Animal Physiology, 5th ed.) – Figure 13.19

20 Respiratory System

Oxygen Transport in Blood:

O2 is carried in two forms in blood: dissolved and bound to hemoglobin

A) Dissolved O2:

Accounts for 2% of total O2 content of blood

Henry’s Law: Recall: CX = PX x Solubility The concentration of dissolved O is proportional to the partial CX = Concentration of dissolved gas (mL X / 100 mL blood) 2 pressure of O PX = Partial pressure of gas (mm Hg) 2 Solubility = Solubility of gas in blood (mL X / 100 mL / mm Hg) Grossly insufficient to meet the [O ] = P x Solubility demands of the tissues 2 O2

[O2] = 100 x 0.003 At rest, tissues require 250 mL O2 / min [O ] = 0.30 mL / 100 mL blood 2 O2 delivery = CO x [dissolved O2]

O2 delivery = 5.0 L / min x 0.3 mL O2 / 100 mL

O2 delivery = 15 mL O2 / min

Respiratory System

Oxygen Transport in Blood:

O2 is carried in two forms in blood: dissolved and bound to hemoglobin

B) O2 bound to hemoglobin:

Accounts for remaining 98% of total O2 content of blood

Globular protein: 2  & 2  subunits each containing a moiety

• 4 O2 / hemoglobin Iron (ferrous state – Fe2+) bound to nitrogens

3+ Oxyhemoglobin = O2 bound to hemoglobin Shouldn’t O2 oxidize iron (ferric state – Fe )?

Deoxyhemoglobin = No O2 present No – nitrogen bonds prevent this…

Methemoglobin = Iron in ferric (Fe3+) state BUT – if it does happen:

• Does not bind O2 Methemoglobin reductase – reduces Fe3+ to Fe2+

21 Respiratory System

Oxygen Transport in Blood:

O2 is carried in two forms in blood: dissolved and bound to hemoglobin

B) O2 bound to hemoglobin:

Hemoglobin structure demonstrates a developmental shift

Fetal hemoglobin Adult hemoglobin (hemoglobin F - HbF) (hemoglobin A - HbA)

22 22

Hemoglobin F has a higher

affinity for O2 than hemoglobin A, facilitating O2 transfer across the

Respiratory System

Oxygen Transport in Blood:

O2 is carried in two forms in blood: dissolved and bound to hemoglobin

B) O2 bound to hemoglobin:

Amount of O2 bound to hemoglobin determined by the hemoglobin concentration and by the O2-binding capacity of that hemoglobin

O2-binding Capacity: PUTTING IT ALL TOGETHER:

The maximum amount of O2 that can be bound to hemoglobin per volume of blood O2 Content:

(Assumes hemoglobin 100% saturated) The actual amount of O2 per unit volume of blood Under normal conditions: O2 = (O2-binding capacity x % saturation) + • 1.0 g of hemoglobin can bind 1.34 mL 02 content dissolved O2 • [hemoglobin A] = 15 g / 100 mL

THUS O2 Delivery to tissues:

The actual amount of O2 delivered O2-binding capacity = 15 g / 100 mL x 1.34 mL O2 / g HbA to the tissues

O2 O2-binding = Cardiac output x O2 content of blood capacity = 20.1 mL O2 / 100 mL blood delivery

22 Respiratory System Reminder: Oxygen Transport in Blood: Each hemoglobin as the capacity to bind 4 O2 molecules

O2 is carried in two forms in blood: dissolved and bound to hemoglobin

B) O2 bound to hemoglobin:

The % saturation of hemoglobin is a function of the P of blood O2

Sigmoid curve O2-hemoglobin Dissociation Curve: Describe relationship between percent saturation of Hb and partial pressure of oxygen P50 Point at which 50% of Hb saturated THE PERCENT SATURATION OF HEME SITES DOES NOT INCREASE Change in value is LINEARLY AS PO INCREASES an indicator for a 2 change in affinity of Hb for O 2 Sub-unit Cooperativity: ( P =  affinity) 50 Oxygenation of first heme group facilitates oxygenation of other heme groups

Costanzo (Physiology, 4th ed.) – Figure 5.20

Respiratory System

Oxygen Transport in Blood:

O2 is carried in two forms in blood: dissolved and bound to hemoglobin

B) O2 bound to hemoglobin: Under normal, resting conditions, arterial blood hemoglobin is 98% saturated

and only ~ 25% of O2 is unloaded at tissues Small drop in P O2 “wiggle room” equates to large increase in O 2 O unloaded to Points to Ponder: unloading 2 resting tissues 1) Hemoglobin is almost completely saturated at a P of 70 mm Hg O2

Additional O2 ~ complete unloaded to ADAPTIVE SIGNIFICANCE? saturation exercising tissues 2) The unloading of O2 occurs on the steep portion of the dissociation curve

ADAPTIVE SIGNIFICANCE?

Tissues Tissues Lungs (exercising) (at rest) Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.20

23 Respiratory System 2,3-DPG = 2,3-diphosphoglycerate Oxygen Transport in Blood: • Byproduct of RBC glycolysis • Binds to  chains of hemoglobin

O2 is carried in two forms in blood: dissolved and bound to hemoglobin

B) O2 bound to hemoglobin:

The O2-hemoglobin dissociation curve can shift to the right or the left depending on local conditions in the blood

Right shift = Decreased Hb affinity for O2

• Facilitates unloading of O2

A)  P CO2 Bohr B)  pH effect ‘Adaptive Complex’ C) 

Increased P50 D)  2,3-DPG

Influence Hb saturation by modifying hemoglobin’s three-dimensional structure

Costanzo (Physiology, 4th ed.) – Figure 5.22

Respiratory System 2,3-DPG = 2,3-diphosphoglycerate Oxygen Transport in Blood: • Byproduct of RBC glycolysis • Binds to  chains of hemoglobin

O2 is carried in two forms in blood: dissolved and bound to hemoglobin

B) O2 bound to hemoglobin:

The O2-hemoglobin dissociation curve can shift to the right or the left depending on local conditions in the blood

Left shift = Increased Hb affinity for O2

• Hinders unloading of O2

A)  P CO2 B)  pH C)  temperature

Decreased P50 D)  2,3-DPG

Increased affinity of hemoglobin F (fetus) ? due to  2,3-DPG binding ?

Costanzo (Physiology, 4th ed.) – Figure 5.22

24 Respiratory System

Pathophysiology:

Carbon monoxide poisoning is catastrophic

for O2 delivery to tissues

1) CO decreases O2 bound to Hb Example: • CO binds to Hb with an affinity that is

250x greater than that of O2 (forms carboxyhemoglobin)

Left shift “cherry red”

2) CO causes left shift of dissociation curve

• Heme groups not bound to CO have

an increased affinity for O2

Costanzo (Physiology, 4th ed.) – Figure 5.22

Respiratory System

Carbon Dioxide Transport in Blood:

CO2 is carried in three forms in blood: dissolved, bound to - hemoglobin, and as bicarbonate (HCO3 )

A) Dissolved CO2:

Accounts for 5% of total CO2 content of blood

Henry’s Law:

CX = PX x Solubility

CX = Concentration of dissolved gas (mL X / 100 mL blood)

PX = Partial pressure of gas (mm Hg) Solubility = Solubility of gas in blood (mL X / 100 mL / mm Hg)

[CO ] = P x Solubility 2 CO2

[CO2] = 40 x 0.07 (Arterial blood)

[CO2] = 2.80 mL / 100 mL blood

25 Respiratory System

Carbon Dioxide Transport in Blood:

CO2 is carried in three forms in blood: dissolved, bound to - hemoglobin, and as bicarbonate (HCO3 )

B) CO2 bound to hemoglobin:

Accounts for 3% of total CO2 content of blood

Reminder:

The binding of CO2 to hemoglobin causes a conformational change

• CO2 binds to the terminal reducing the affinity of Hb amino groups on globins for O2 (right shift)

IN TURN

When less O2 is bound to Hb, Carbaminohemoglobin = CO2 bound to hemoglobin the affinity of Hb for CO2 increases (the Haldane effect)

Respiratory System

Carbon Dioxide Transport in Blood:

CO2 is carried in three forms in blood: dissolved, bound to - hemoglobin, and as bicarbonate (HCO3 )

- C) CO2 converted to HCO3 : Plasma Accounts for remaining 92% of total CO2 content of blood

Diffuses into (contributes to REVERSABLE RBCs CA the ) + - CO2 + H20 H2CO3 H + HCO3

1) Carbon dioxide (CO2) combines with water (H2O) to form carbonic acid (H2CO3) • Reaction catalyzed by (CA)

+ - 2) H2CO3 dissociates into hydrogen ion (H ) and bicarbonate ion (HCO3 ) - • HCO3 released into plasma • H+ buffered in RBC by deoxyhemaglobin

26 Respiratory System

Carbon Dioxide Transport in Blood:

CO2 is carried in three forms in blood: dissolved, bound to - hemoglobin, and as bicarbonate (HCO3 )

- C) CO2 converted to HCO3 :

Accounts for remaining 92% of total CO2 content of blood

Chloride shift: To maintain charge balance in RBCs, - - a Cl is exchanged with a HCO3 as - the HCO3 the cell • Band three protein functions as passive transporter

Costanzo (Physiology, 4th ed.) – Figure 5.24

Respiratory System

Gas Transport - Review:

Tissue – Blood Interface:

Randall et al. (Eckert Animal Physiology, 5th ed.) – Figure 13.10

27 Respiratory System Note: Gas Transport: Carbonic anhydrase also embedded in respiratory membrane Lung – Blood Interface:

Randall et al. (Eckert Animal Physiology, 5th ed.) – Figure 13.10

Respiratory System Recall: The carries blood from Ventilation / Perfusion Relationships: the right ventricle and returns blood to the left atrium

Pulmonary blood flow is regulated primarily by altering the resistance of the

Mechanisms of Regulation:

A) Partial pressure of alveolar O2 B) Vasoactive Chemicals

Reduces pulmonary Hypoxic  PA flow to poorly O2 ventilated alveoli Vasoconstrict vessel

Thromboxane A2 Mechanism of Action: Source: Action: Vasoconstriction • If PA falls below 70 mm Hg, voltage-gated O2 Prostacyclin 2+ Ca gates open in vascular smooth muscle, leading to contraction Source: Endothelium Action: Vasodilator

Can act locally (blocked alveolus) or globally (high altitude)

28 Respiratory System

Ventilation / Perfusion Relationships:

The distribution of pulmonary blood flow with the lung is uneven due to the effects of gravity

Zone 1: Apex of lung Low blood Gravitational flow Effect Palveoli > Parterial > Pvein • Pulmonary capillaries compressed Lower vessel pressures by surrounding alveoli

Zone 2: Middle of lung Medium blood flow Parterial > Palveoli > Pvein • Minimal compression; blood flow driven

by Partial vs. Palveoli difference

Zone 3: Base of lung High blood flow Parterial > Pvein > Palveoli • The greatest number of capillaries open; Higher vessel high arterial and venous pressures pressures

Randall et al. (Eckert Animal Physiology, 5th ed.) – Figure 13.26

Respiratory System

Control of Breathing:

Breathing is regulated so the lungs can maintain the Pa and Pa within a normal range O2 CO2

Amphetamines / Caffeine: Medullary Respiratory Centers:  activity 1) Ventral Respiratory Group PRCs • Inspiratory center Oscillating rhythm of neuronal firing / quiescence • ‘Pacesetter’ (12 – 15 breaths / min) VRG

2) Dorsal Respiratory Group Barbiturates / Opiates / Alcohol: • Expiratory center  respiratory center activity • Active during forced exhalation

DRG Pontine Respiratory Centers: 1) Apneustic Center Intercostal • Triggers prolonged inspiratory gasps Phrenic 2) Pneumotaxic Center • Turns off inspiration • Limits size of tidal volume

Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.23

29 Respiratory System

Control of Breathing:

Depth and rate of breathing can be modified in response to changing demands on the body

Most important factors regulating ventilation are chemical

Peripheral (+) • (IX) (+) • Aortic arch (X) (CSF)

Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.24

Respiratory System

Control of Breathing:

Hypercapnia: Increased PCO2 in arterial blood Chemical Factors: : Decreased PCO2 in arterial blood A) P CO2 • Most potent respiratory stimulant (maintained @  3 mm Hg) • Mediated via central / peripheral chemoreceptors

Can cross blood-brain barrier

Can not cross blood-brain barrier

 CO2 =  ventilation

 CO2 =  ventilation

Ultimately leads to change in pH of cerebral spinal fluid

Costanzo (Physiology, 4th ed.) – Figure 5.32

30 Respiratory System

Control of Breathing: Chemical Factors: A) P CO2 • Most potent respiratory stimulant (maintained @  3 mm Hg) • Mediated via central / peripheral chemoreceptors

B) P Issue for individuals O2 with COPD: • Minor respiratory stimulant ( O2 =  ) Continual high levels of • Mediated via peripheral chemoreceptors P in system results in CO2 • Stimulated by P < 60 mm Hg in arterial blood P taking over regulation O2 O2

C) Arterial pH IF RESPIRATORY DISTRESS OCCURS • Independent of changes in arterial P CO2 • Compensatory mechanism for metabolic acidosis • Mediated by peripheral chemoreceptors (carotid body only)

Respiratory System

Control of Breathing:

Depth and rate of breathing can be modified in response to changing demands on the body

Addition factors contribute to ventilation regulation

Hering-Breuer Reflex: When lung / airways stretched, inspiratory center inhibited Lung stretch Peripheral receptors chemoreceptors (+) • Carotid body (IX) (+) Vagus (X) • Aortic arch (X) (CSF) (-) nerve Central chemoreceptors (+)

Function in anticipatory / muscle response to exercise stretch receptors

Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.24

31 Respiratory System Laryngeal spasm Control of Breathing: (e.g., sarin gas)

Depth and rate of breathing can be modified in response to changing demands on the body

Addition factors contribute to ventilation regulation

Lung Nasal cavity = stretch Lower conduction system = receptors (+) (cessation of breathing) (+) Vagus (X) (CSF) (-) nerve Central (-) chemoreceptors (+) closes; Irritant thoracic cavity shrinks receptors Joint / muscle stretch receptors Epiglottis opens; air forcefully released (~ 100 mph) Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.24

Respiratory System

Control of Breathing:

Depth and rate of breathing can be modified in response to changing demands on the body Higher control centers; Voluntary control over breathing Addition factors contribute to ventilation regulation

Hypoventilation: Decrease breathing rate / depth / emotional stimuli (+ / -) acting through hypothalamus :

(+ / -) Increase breathing rate / depth Lung Rate / depth of respiration stretch exceeds demands for receptors O2 delivery / CO2 removal (+)

(+) Vagus (X) (CSF) (-) nerve Central (-) chemoreceptors (+) Irritant receptors Joint / muscle stretch receptors

Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.24

32 Respiratory System

formaldehyde benzene vinyl chloride arsenic ammonia hydrogen cyanide

~ 3,400 deaths / year contributed to second- hand smoke…

Increase in 1900 = Rare… rates correlated with rise 1956 = 29,000 deaths in smoking among adult 1978 = 105,000 deaths men and women 2004 = 160,440 deaths

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