Respiratory System - Western Oregon Universitywou.edu/~lemastm/Teaching/BI336/Respiratory System (3).pdf · Respiratory System For the body to survive, there must be a constant supply

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:

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

1

Provides surface area for

gas exchange (between air / blood)

Moves air to / from gas

exchange surface

3

2

Protects system (debris / pathogens / dessication)

4 Produces sound (vocalization)

Assists in the detection

of odorants

5

Upper Respiratory

System

Lower Respiratory

System • Filters / warms / humidifies

incoming air

• Conduction of air

• Gas exchange

1) External nares

2) Nasal cavity

• Resonance chamber

3) Uvula

5) Larynx

• Provide open airway

• channel air / food

Epiglottis

4) Pharynx

• Nasopharynx

• Oropharynx

• Laryngopharynx

7) Bronchial tree

• voice production

8) Alveoli

Respiratory System

Functional Anatomy:

(link)

6) Trachea

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

http://www.gastrolab.net/ya494x.jpg

http://www.youtube.com/watch?v=ajbcJiYhFKY

2

Trachea

Primary

Bronchus

Bronchi

bifurcation (23 orders)

Naming of pathways:

• > 1 mm diameter = bronchus

• < 1 mm diameter = bronchiole

• < 0.5 mm diameter = terminal bronchiole

Bronchiole Terminal Bronchiole

Respiratory Bronchiole Alveolus

Green = Conducting zone

Purple = Respiratory zone

Respiratory System

Functional Anatomy:


Respiratory Mucosa / Submucosa:

Near

trachea Near

alveoli

Epithelium:

Pseudostratified

columnar

Simple

cuboidal

Lamina Propria (areolar tissue layer):

Cilia No cilia

smooth

muscle

smooth

muscle

Cartilage:

Rings Plates / none

Mucosa:

Mucous membrane

(epithelium / areolar tissue)

Mucous

glands

No

mucous

glands

Respiratory System

Functional Anatomy:


How are inhaled debris / pathogens cleared from respiratory tract?

Macrophages

Nasal Cavity:

Particles > 10 µm

Conducting Zone:

Particles 5 – 10 µm

Respiratory Zone:

Particles 1 – 5 µm Mucus Escalator

Respiratory System

Functional Anatomy:


http://www.sciencephoto.com/image/308007/large/P4100031-3-D_CT_scan_of_the_conchae_in_the_nasal_sinuses-SPL.jpg

3

Respiratory System

Functional Anatomy:


Esophagus

Tough,

flexible tube (~ 1” diameter) 15 – 20 tracheal

cartilages

• Protect airway

Pseudostratified ciliated

columnar epithelium

Goblet cells:

Unicellular mucous

secreting glands

(C-shaped)

Trachea

• Allow for food passage

Respiratory System

Functional Anatomy:


Right primary bronchus

wider, shorter & steeper

( blockage hazard)

• 1º = Extrapulmonary bronchi

• 2º = Intrapulmonary bronchi

Bronchus

Pseudostratified

ciliated columnar

epithelium

Smooth muscle

Cartilage plate

Bronchitis:

Inflammation of airways

(> 1 mm diameter)

Respiratory System

Functional Anatomy:


Bronchiole

(< 1 mm diameter)

Pseudostratified

ciliated columnar

epithelium

Thick

smooth muscle

Cartilage

plates?

Mucous glands rare – Why?

Sympathetic stimulation (NE; 2 receptors)

• Leads to bronchodilation

Parasympathetic stimulation (ACh; muscarinic receptors)

• Leads to bronchoconstriction

E (medulla) triggers

response

Allergic attack = Histamine = Bronchoconstriction

Synthetic drugs (e.g., albuterol)

trigger response

Alveoli

(300 million / lung)

4

Respiratory System

Functional Anatomy:

200 m

Type I Pneumocytes:

Type II Pneumocytes:

Alveolar

sac

Total surface area:

75 - 90 m2 (~1/2 tennis court)

Alveolar

pores

Terminal

bronchiole

Respiratory

bronchiole

Alveolar macrophages:

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

Surrounded by fine

elastic fibers

• Simple squamous; forms wall of alveoli

• Alveolar pores (1 – 6 / alveoli)

• Cuboidal / round; secrete surfactant

• Reduces surface tension (stops alveoli collapse)

• Clear debris on alveolar surface

Respiratory Membrane:

1) Type I pneumocytes

2) Endothelial cells of capillaries

3) Fused basement membranes

0.1 – 0.5 m thick

Pneumonia:

Thickening of respiratory membrane

Respiratory System

Functional Anatomy:

Gas exchange occurs readily in the alveoli of the lung via

simple diffusion across the respiratory membrane


Respiratory Physiology:

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

2) External respiration (gas exchange @ blood-gas barrier)

3) Transport of respiratory gases (blood)

4) Internal respiration (gas exchange @ tissues)

Respiratory System

Respiration includes: 1

2

3

4

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

5

Pulmonary Ventilation:

Trachea

Thoracic

wall

Visceral

pleura

Parietal

pleura

Pleural

cavity

Lung

Diaphragm Diaphragm

Simplified Model:

Trachea

Lung

Pleural

cavity

Thoracic

wall

Respiratory System


Pressure relationships in the thoracic cavity:

Atmospheric pressure = ~ 760 mm Hg

(Consider Patmospheric = 0 mm Hg)

1) Intrapulmonary Pressure (w/in the alveoli):

• Static conditions = 0 mm Hg

2) Intrapleural pressure (w/in pleural cavity):

• Always relatively negative (~ - 4 mm Hg)

atmospheric pressure = Patm = 0 mm Hg

Intrapleural pressure (Pip = - 4 mm Hg)

Diaphragm

Intrapulmonary

pressure (Ppul = 0 mm Hg)

• Inhalation (inspiration) = Ppul slightly negative

• Exhalation (expiration) = Ppul slightly positive

• Prevents lungs from collapsing

Respiratory System


Why is the intrapleural pressure negative?

Answer: Interaction of opposing forces

Forces acting to collapse lung:

1) Elasticity of lungs

2) Alveolar surface tension

Force resisting lung collapse:

1) Elasticity of chest wall

Surface tension of

serous fluids keep

lungs “stuck” to

chest wall

Forces equilibrate at Pip = - 4 mm Hg

Respiratory System

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


6

CHANGING THE VOLUME RESULTS IN INVERSE

CHANGE OF PRESSURE

P = pressure of gas (mm Hg)

V = volume of gas (mm3)

P1 = initial pressure; V1 = initial volume

P2 = resulting pressure; V2 = resulting volume

Boyle’s Law:

P1V1 = P2V2

Example: 4 mm Hg (2 mm3) = P2 (4 mm3) P2 = 2 mm Hg

Pulmonary ventilation is a mechanical process that depends on

thoracic cavity volume changes

Respiratory System



Inspiration:

Muscular expansion of thoracic cavity

Diaphragm

0 mm Hg

0 mm Hg

- 4 mm Hg

A) Contraction of diaphragm

• Lengthens thorax (pushes liver down)

B) Contraction of external intercostal muscles

• Widens thorax

Respiratory System





Inspiration:

Muscular expansion of thoracic cavity

Diaphragm

- 1 mm Hg

0 mm Hg

- 6 mm Hg

A) Contraction of diaphragm

• Lengthens thorax (pushes liver down)

B) Contraction of external intercostal muscles

• Widens thorax

Respiratory System



Results in:

• Reduced intrapleural pressure (Pip)

• Reduced intrapulmonary pressure (Ppul)

Results in decreased pressure in thoracic

cavity and air enters


7

0 mm Hg

Respiratory System



Expiration:

Retraction of thoracic cavity

A) Passive Expiration

• Diaphragm / external intercostals relax

• Elastic rebound (lungs rebound)

- 4 mm Hg

0 mm Hg +1 mm Hg

Diaphragm

Results in increased pressure

in thoracic cavity; air exits

B) Active (“Forced”) Expiration

• Abdominal muscles contract

• Internal intercostals contract


Eupnea:

Quiet breathing

(active inspiration;

(passive expiration)

Hyperpnea:

Forced breathing

(active inspiration;

(active expiration)

Internal pressure

can reach +100 mm Hg

(e.g., why you should exhale when lifting weights)


Respiratory System



A) Airway resistance

Respiratory System


Several physical factors exist influence pulmonary ventilation

Q = P / R

Q = Airflow (L / min)

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

Poiseuille’s Law:

R = 8Lη

r4

R = Resistance

η = Viscosity of inspired air

L = Length of airway

r = Radius of airway

Why don’t the smallest airways provide

the highest resistance?

Reminder:

Parasympathetic system produces

bronchial constriction

Sympathetic system produces

bronchial dilation

( diameter = resistance)

( diameter = resistance)

Resis

tan

ce

Bifurcation stage

Medium-sized

bronchi

Terminal

bronchioles

8

B) Surface tension in alveoli

Respiratory System



Surface tension generated as neighboring liquid molecules on the surface

of alveoli are drawn together by attractive forces

P = 2T

r Law of Laplace:

P = Collapsing pressure on alveolus (dynes / cm2)

T = Surface tension (dynes / cm)

r = Radius of alveolus (cm)

Pressure required to

keep alveolus open

Problem?

Respiratory Distress Syndrome

(e.g., pre-mature babies)

Dipalmitoyl

phosphatidylchorine

(DPPC)

Surfactant

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

C) Lung compliance

Respiratory System



Measure of change in lung volume that occurs with a given

transpulmonary pressure

CL = VL

(Ppul – Pip)

CL = Lung compliance (cm3 / mm Hg)

VL = Lung volume (cm3)

Ppul = Intrapulmonary pressure (mm Hg)

Ppi = Intrapleural pressure (mm Hg)

(Transmural pressure)

The higher the lung compliance, the easier

it is to expand the lungs at a given pressure

Determined by:

1) Elasticity of lung

2) Surface tension

Emphysema:

Increased lung compliance due

to loss of elastic fibers

Barrel Chest

Fibrosis:

Decreased lung compliance due

to scar tissue build-up

Respiratory Volumes / Capacities:

Tidal Volume:

Amount of air moved into / out of

lung during single respiratory cycle

(spirometric reading)

Resting Tidal Volume (~ 500 ml)

Inspiratory reserve

Volume (IRV) (~ 3100 ml)

Expiratory reserve

volume (~ 1200 ml)

Residual volume (~ 1200 ml)

Vital capacity (~ 4800 ml)

Total lung

capacity (~ 6000 ml)

(Male)

(Female ~ 4200 ml)

Respiratory System



Inspiratory


Functional

residual


Increases with:

• Body size

• Gender

• Conditioning

Decreases with:

• Age

9

Pathophysiology:

Cardiovascular System – Vessels

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

0.8

FEV1

FVC

• Both FEV1 and FVC low but

FEV1 decreased more than

FVC

< 0.8

• Both FEV1 and FVC low but

FVC decreased more than

FEV1

> 0.8

Respiratory System


Not all inhaled air participates in gas exchange; this

volume is referred to as dead space


Rule of Thumb:

Anatomical dead space in a healthy

young adult is equal to 1 ml / pound

of ideal body weight

Physiologic Dead Space:

Anatomic dead space plus any

ventilated alveoli that might not

participate in gas exchange

Anatomic Dead Space:

Volume of air found in the

conducting airways, including

the nose bronchioles

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

= 12 breaths / minute x 500 mL

= 6000 mL / minute

Minute Volume:

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

= 12 breaths / minute x (500 mL - 150 mL)

= 4200 mL / minute

Alveolar Ventilation:

Available for

gas transfer…

= 6.0 liters / minute

= 4.2 liters / minute

Respiratory System


Ventilation rate is the volume of air moved into an out of

the lungs per unit time

(or physiologic dead space)

10






Respiratory System


2

3

4


Respiratory System


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

% Composition of Atmospheric Air

21%

O2

79%

N2

Patmosphere:

760 mm Hg

For dry gases:

PX = PB x F

PX = Partial pressure of gas (mm Hg)

PB = Barometric pressure (mm Hg)

F = Fractional concentration of gas

PO2 = 760 x 0.21

PO2 = 160 mm Hg

Respiratory System

Gas Exchange:




A) Dalton’s Law of Partial Pressures:

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

% Composition of Atmospheric Air

21%

O2

79%

N2

Patmosphere:

760 mm Hg

For humidified gases:

PX = (PB – PH2O) x F


PB = Barometric pressure (mm Hg)

PH2O = Water vapor pressure at 37C (47 mm Hg)

F = Fractional concentration of gas

PO2 = (760 – 47) x 0.21

PO2 = 150 mm Hg

11

Respiratory System




B) Henry’s Law:

Gases in a mixture dissolve in a liquid in proportion to their partial pressures

Note:

At equilibrium, the partial pressure

of a gas in the liquid phase equals

the partial pressure in the gas phase

CX = PX x Solubility

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


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

Solubility:

How much of a gas will dissolve in a

liquid at a given partial pressure

[O2] = PO2 x Solubility

[O2] = 150 x 0.003

[O2] = 0.45 mL / 100 mL blood

CO2 >> O2 >> N2

(the “bends”)

Gas Exchange:

Respiratory System


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

VX = Volume of gas transferred per unit time

D = Diffusion coefficient of the gas (includes solubility)

A = Surface area

P = Partial pressure difference of the gas

X = Thickness of the membrane

VX = DAP

x The driving force for diffusion of a gas is the

partial pressure difference of the gas,

not the concentration difference

PO2

in lung

PO2

in blood 100 40

60

Gas Exchange:

directly proportional

inversely proportional

Respiratory

membrane



Respiratory System

Gas Exchange:

Unlike alveolar air, where there is only one form of gas,

blood is able to carry gases in addition forms

PX

Dissolved gas Bound gas Chemically

modified gas The higher the solubility

of a gas, the higher the

concentration of the gas

in solution

Gases bind directly

to plasma proteins or

to hemoglobin

Gases react with blood

components to form

new products

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

In solution, only dissolved gases

contribute to partial pressures

12

Respiratory System

Gas Exchange:

Gas transport in the lungs:


Respiratory System

Gas Exchange:

Gas transport in the lungs:


PX = PB x F

PX = (PB – PH2O) x F Lung air modified by gas exchange:

O2 = 21%

CO2 = 0%

O2 = 21%

CO2 = 0%

O2 = 14%

CO2 = 6%

PX = (PB – PH2O) x F

Composition reflects

metabolic activity of body

Due to rapid diffusion

of gases, equilibrium reached

Patmosphere:

760 mm Hg

The amount of O2 / CO2

transferred corresponds to the

needs of the body

1:1 exchange rate

PO2 = 60

PCO2 = 6

?

VX = DAP

x

Diffusional coefficient 20x greater

for CO2 than for O2

Systemic tissues undergo

reversal of pattern observed at lung

1) O2 into blood; CO2 out of blood

2) Mixture of fresh and residual air

Respiratory System

Gas Exchange:

Gas exchange across the alveolar / pulmonary capillary barrier is

described as either diffusion-limited or perfusion-limited

Diffusion-limited:

The total amount of gas transported

across the alveolar / capillary barrier is

limited by the diffusional process

Partial pressure

gradient maintained across

entire length of capillary

(gas does not equilibrate)

Perfusion-limited:

The total amount of gas transported

across the alveolar / capillary barrier is

limited by blood flow

Example:

Carbon

monoxide

Example:

Nitrous

oxide Partial pressure

gradient not maintained

across length of capillary

(gas equilibrates)


gas transport = diffusion rate gas transport = blood flow

13

Respiratory System

Gas Exchange:

Under normal conditions, O2 transport into pulmonary capillaries

is a perfusion-limited process


Rest Exercise “wiggle room”

End of

capillary

Start of

capillary

Time in pulmonary capillary (s)

PO

2 (

mm

Hg)

PO2 does not equilibrate until

hemoglobin saturated

Remember:

PO2 only measures free

O2 concentration

Respiratory System

In certain pathologic conditions, O2 transport

becomes diffusion limited

Pathophysiology:

Lung fibrosis


Alveolar wall thickens; slows

down diffusion rate

PO2 equilibrium never

reached

Outcome:

Decreased PO2 in systemic

arterial blood, especially

during physical activity

VX = DAP

x

Respiratory System


VX = DAP

x

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 oxygen transport

into pulmonary capillaries for A) PaO2,

B) rate, and C) exercise

Rest Exercise

“shortness

of breath”

Driving force:

50 – 25 = 25 mm Hg

14






Respiratory System


2

3

4


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

Recall:

The concentration of dissolved

O2 is proportional to the partial

pressure of O2

Henry’s Law:

[O2] = PO2 x Solubility

[O2] = 100 x 0.003

[O2] = 0.30 mL / 100 mL blood

Grossly insufficient to meet the

demands of the tissues

At rest, tissues require 250 mL O2 / min

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



B) O2 bound to hemoglobin:

Accounts for remaining 98% of total O2 content of blood

Globular protein:

2 & 2 subunits each

containing a heme moiety

• 4 O2 / hemoglobin

Oxyhemoglobin = O2 bound to hemoglobin

Iron (ferrous state – Fe2+)

bound to nitrogens

Deoxyhemoglobin = No O2 present

Shouldn’t O2 oxidize iron (ferric state – Fe3+ )?

No – nitrogen bonds prevent this…

Methemoglobin reductase – reduces Fe3+ to Fe2+

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

• Does not bind O2

15

Respiratory System




Hemoglobin structure demonstrates a developmental shift

Adult hemoglobin (hemoglobin A - HbA)

22

Fetal hemoglobin (hemoglobin F - HbF)

22

Hemoglobin F has a higher

affinity for O2 than hemoglobin A,

facilitating O2 transfer across

the placenta

Respiratory System




Amount of O2 bound to hemoglobin determined by the hemoglobin concentration

and by the O2-binding capacity of that hemoglobin

O2-binding Capacity:

The maximum amount of O2 that can be

bound to hemoglobin per volume of blood

(Assumes hemoglobin 100% saturated)

Under normal conditions:

• 1.0 g of hemoglobin can bind 1.34 mL 02

• [hemoglobin A] = 15 g / 100 mL

THUS

O2-binding

capacity = 15 g / 100 mL x 1.34 mL O2 / g HbA

O2-binding

capacity = 20.1 mL O2 / 100 mL blood

O2 Content:

The actual amount of O2 per unit

volume of blood

O2

content = (O2-binding capacity x % saturation) +

dissolved O2

O2 Delivery to tissues:

The actual amount of O2 delivered

to the tissues

O2

delivery = Cardiac output x O2 content of blood

PUTTING IT ALL TOGETHER:

Respiratory System




The % saturation of hemoglobin is a function of the PO2 of blood

Reminder:

Each hemoglobin as the capacity to

bind 4 O2 molecules

O2-hemoglobin Dissociation Curve:

Describe relationship between percent saturation

of Hb and partial pressure of oxygen

Sub-unit Cooperativity:

Oxygenation of first heme group facilitates

oxygenation of other heme groups

Sigmoid curve

THE PERCENT SATURATION OF

HEME SITES DOES NOT INCREASE

LINEARLY AS PO2 INCREASES

P50

Point at which 50%

of Hb saturated

Change in value is

an indicator for a

change in affinity

of Hb for O2

( P50 = affinity)


16

Respiratory System




Under normal, resting conditions, arterial blood hemoglobin is 98% saturated

and only ~ 25% of O2 is unloaded at tissues


Points to Ponder:

1) Hemoglobin is almost completely saturated

at a PO2 of 70 mm Hg

~ complete

saturation

“wiggle room”

ADAPTIVE SIGNIFICANCE?

2) The unloading of O2 occurs on the steep

portion of the dissociation curve

Lungs Tissues

(at rest)

ADAPTIVE SIGNIFICANCE?

O2 unloaded to

resting tissues

Additional O2

unloaded to

exercising

tissues

Tissues

(exercising)

Small drop in PO2 equates to large

increase in O2

unloading

Respiratory System




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

Increased P50

• Facilitates unloading of O2

A) PCO2

B) pH ‘Adaptive Complex’

2,3-DPG = 2,3-diphosphoglycerate

• Byproduct of RBC glycolysis

• Binds to chains of hemoglobin

Influence Hb saturation by modifying

hemoglobin’s three-dimensional structure

Bohr

effect

C) temperature

D) 2,3-DPG

Respiratory System




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

Decreased P50

• Hinders unloading of O2

A) PCO2

B) pH

C) temperature

D) 2,3-DPG

2,3-DPG = 2,3-diphosphoglycerate

• Byproduct of RBC glycolysis

• Binds to chains of hemoglobin

Increased affinity of hemoglobin F (fetus)

due to 2,3-DPG binding ? ?

17

Respiratory System

Pathophysiology:

Carbon monoxide poisoning is catastrophic

for O2 delivery to tissues


1) CO decreases O2 bound to Hb

• CO binds to Hb with an affinity that is

250x greater than that of O2

(forms carboxyhemoglobin)

Example:

“cherry red”

2) CO causes left shift of dissociation curve

• Heme groups not bound to CO have

an increased affinity for O2

Left shift

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:

[CO2] = PCO2 x Solubility

[CO2] = 40 x 0.07

[CO2] = 2.80 mL / 100 mL blood

(Arterial blood)

Respiratory System




B) CO2 bound to hemoglobin:

Accounts for 3% of total CO2 content of blood

• CO2 binds to the terminal

amino groups on globins

Carbaminohemoglobin = CO2 bound to hemoglobin

Reminder:

The binding of CO2 to hemoglobin

causes a conformational change

reducing the affinity of Hb

for O2 (right shift)

IN TURN

When less O2 is bound to Hb,

the affinity of Hb for CO2 increases

(the Haldane effect)

18

Respiratory System




C) CO2 converted to HCO3- :

Accounts for remaining 92% of total CO2 content of blood

+ CO2 H20 H2CO3 H+ + HCO3-

CA

Plasma

1) Carbon dioxide (CO2) combines with water (H2O) to form carbonic acid (H2CO3)

• Reaction catalyzed by carbonic anhydrase (CA)

2) H2CO3 dissociates into hydrogen ion (H+) and bicarbonate ion (HCO3- )

• HCO3- released into plasma

Diffuses into

RBCs

• H+ buffered in RBC by deoxyhemaglobin

(contributes to

the Bohr effect) REVERSABLE

Respiratory System




C) CO2 converted to HCO3- :

Accounts for remaining 92% of total CO2 content of blood


To maintain charge balance in RBCs,

a Cl- is exchanged with a HCO3- as

the HCO3- leaves the cell

Chloride shift:

• Band three protein functions

as passive transporter

Respiratory System Respiratory System

Gas Transport - Review:

Tissue – Blood Interface:


19

Respiratory System

Gas Transport:

Lung – Blood Interface:


Note:

Carbonic anhydrase also embedded

in respiratory membrane

Respiratory System

Ventilation / Perfusion Relationships:

Pulmonary blood flow is regulated primarily by altering

the resistance of the arterioles

Recall:

The pulmonary circulation carries blood from

the right ventricle and returns blood

to the left atrium

Mechanisms of Regulation:

A) Partial pressure of alveolar O2

PAO2

Vasoconstrict

vessel

Hypoxic

vasoconstriction

Reduces pulmonary

flow to poorly

ventilated alveoli

Mechanism of Action:

• If PAO2 falls below 70 mm Hg, voltage-gated

Ca2+ gates open in vascular smooth muscle,

leading to contraction

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

B) Vasoactive Chemicals

Thromboxane A2

Source: Endothelium

Action: Vasoconstriction Prostacyclin

Source: Endothelium

Action: Vasodilator

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

Palveoli > Parterial > Pvein Gravitational

Effect

Lower vessel

pressures

Higher vessel

pressures

• Pulmonary capillaries compressed

by surrounding alveoli

Zone 2: Middle of lung

Parterial > Palveoli > Pvein

• Minimal compression; blood flow driven

by Partial vs. Palveoli difference

Low blood

flow

Medium blood

flow

Zone 3: Base of lung

Parterial > Pvein > Palveoli

• The greatest number of capillaries open;

high arterial and venous pressures

High blood

flow


//upload.wikimedia.org/wikipedia/commons/0/09/Thromboxane_A2_acsv.svg

//upload.wikimedia.org/wikipedia/commons/3/3f/Prostacyclin-2D-skeletal.png

20

Respiratory System

Control of Breathing:

Breathing is regulated so the lungs can maintain the

PaO2 and PaCO2

within a normal range

1) Ventral Respiratory Group

2) Dorsal Respiratory Group

VRG

Medullary Respiratory Centers:

Oscillating rhythm of neuronal

firing / quiescence

DRG

Barbiturates / Opiates / Alcohol:

respiratory center activity

1) Apneustic Center

2) Pneumotaxic Center

Pontine Respiratory Centers:

Amphetamines / Caffeine:

respiratory center activity

PRCs

Phrenic nerve

Intercostal

nerves


• Inspiratory center

• ‘Pacesetter’ (12 – 15 breaths / min)

• Expiratory center

• Active during forced exhalation

• Triggers prolonged inspiratory gasps

• Turns off inspiration

• Limits size of tidal volume

Respiratory System


Depth and rate of breathing can be modified in response

to changing demands on the body


Most important factors regulating

ventilation are chemical

• Carotid body (IX)

• Aortic arch (X)

Peripheral

chemoreceptors

Central

chemoreceptors

(CSF)

(+)

(+)

• Most potent respiratory stimulant (maintained @ 3 mm Hg)

Chemical Factors:

Respiratory System

Control of Breathing: Hypercapnia: Increased PCO2 in arterial blood

Hypocapnia: Decreased PCO2 in arterial blood

Can not cross

blood-brain barrier

Can cross

blood-brain barrier

Ultimately leads to change in

pH of cerebral spinal fluid

CO2 = ventilation

CO2 = ventilation

A) PCO2


• Mediated via central / peripheral chemoreceptors

21

• Most potent respiratory stimulant (maintained @ 3 mm Hg)

• Mediated via central / peripheral chemoreceptors

A) PCO2

Chemical Factors:

Respiratory System


B) PO2

• Minor respiratory stimulant ( O2 = respiratory rate)

• Mediated via peripheral chemoreceptors

• Stimulated by PO2 < 60 mm Hg in arterial blood

C) Arterial pH

• Independent of changes in arterial PCO2

• Compensatory mechanism for metabolic acidosis

Issue for individuals

with COPD:

Continual high levels of

PCO2 in system results in

PO2 taking over regulation

IF RESPIRATORY DISTRESS

OCCURS

• Mediated by peripheral chemoreceptors (carotid body only)

Respiratory System





• Carotid body (IX)

• Aortic arch (X)

Peripheral

chemoreceptors

Central

chemoreceptors

(CSF)

Lung

stretch

receptors

Hering-Breuer Reflex:

When lung / airways stretched,

inspiratory center inhibited

(-)

(+)

Joint / muscle

stretch

receptors

Function in anticipatory

response to exercise

Addition factors contribute to

ventilation regulation

(+)

(+) Vagus (X)

nerve

Respiratory System







Central

chemoreceptors

(CSF)

Lung

stretch

receptors

(-)

(+)

Joint / muscle

stretch

receptors

(+)

(+)

Apnea (cessation of breathing)

Epiglottis closes;

thoracic cavity shrinks

Nasal cavity = Sneeze

Lower conduction system = Cough

Epiglottis opens;

air forcefully released (~ 100 mph)

Irritant

receptors

(-)

Vagus (X)

nerve

Laryngeal

spasm

(e.g., sarin gas)

22

Respiratory System







Central

chemoreceptors

(CSF)

Lung

stretch

receptors

(-)

(+)

Joint / muscle

stretch

receptors

(+)

(+)

Irritant

receptors

(-)

Vagus (X)

nerve

Pain / emotional stimuli

acting through hypothalamus

(+ / -)

Higher control centers;

Voluntary control over breathing

(+ / -)

Hypoventilation:

Decrease breathing rate / depth

Hyperventilation:

Increase breathing rate / depth

Rate / depth of respiration

exceeds demands for

O2 delivery / CO2 removal

1900 = Rare…

1956 = 29,000 deaths

1978 = 105,000 deaths

2004 = 160,440 deaths

Increase in lung cancer

rates correlated with rise

in smoking among adult

men and women

formaldehyde

benzene

vinyl chloride

arsenic ammonia

hydrogen cyanide

~ 3,400 deaths / year

contributed to second-

hand smoke…

Respiratory System

Documents

Respiratory System - Western Oregon Universitywou.edu/~lemastm/Teaching/BI336/Respiratory System (3).pdf · Respiratory System For the body to survive, there must be a constant supply