Respiration

ChongQing Medical University physiology department Teacher: Feng Min ()

1Outline

(1) concept
- Respiration : The gas exchange between the body and the external environment.

(2) function
- To absorb O2 , to discharge CO2 ; ensure gaseous metabolism keep balance ; regulate acid-base balance

(3) basic component events

- external respiration: pulmonary ventilation and

gas exchange in the lungs
(pulmonary ventilation: the inflow and outflow of air between the atmosphere
and the lung alveoli)

(gas exchange in the lungs: diffusion of O2 and CO2 between the alveoli and
blood)

- gas transport: transport O

fluid to and from the cells

and CO2 in the blood and body

- Internal respiration: the gas exchange between the blood

and tissues, including cellular respiration

2pulmonary ventilation

Concept: the inflow and outflow of air between the

atmosphere and the lung alveoli

Organs of pulmonary ventilation:

- Airway, lung alveoli, thoracic cage
Airway: nostril, mouth, pharynx, larynx, trachea, bronchus

- Lung alveoli: tiny hollow sacs compose the lung. In the alveoli, gas exchange with the blood. - Thoracic cage: the sternum in front, the spinal column in back, the ribs encircling the chest, the diaphragm below. The act of breathing is performed by enlarging and contracting the ~.

Functions of the airway: Upper airways (from nose to larynx) : Warming the air; humidifying the air; cleansing the air;

Trachea, major bronchus, bronchioles, terminal bronchioles: Provides a low resistance pathway for air flow;

Respiratory bronchioles, alveolar ducts, alveoli: gas exchange with the blood.

Thoracic cage and lungs

Thoracic cage structure:

- The lungs are enclosed in the thoracic cage, which is composed of the sternum in front, the spinal column in back, the ribs encircling the

chest, and diaphragm below.

Pleural sac:
- Each lung is surrounded by a completely closed pleural sac. The two sacs are separated from each other. The visceral pleura is firmly attached to the lung; the outer layer (that is called parietal pleura) is attached to the interior thoracic wall and diaphragm. The two layers of pleura are not attached to each other, they are separated by an very thin layer of intrapleural fluid.

The functions of the intrapleural fluid :

- Lubricate the pleural surface, so the friction of the two layers of pleura is very small, then the pleura can slide freely; - Cohesion of the fluid molecules attach two layers of pleura together, that means the lungs and the thoracic wall are attached together by intrapleural fluid, so any change in the volume of the thoracic cage is immediately reflected by a similar change in the volume of the lungs.

The power of pulmonary ventilation

1outline
- Direct power: pressure difference between outside air pressure and intrapulmonary pressure. - Primitive power: the contraction and relaxation of the respiratory

muscles.

2respiratory movement
- (1) concept: the contraction and relaxation of the respiratory muscles
cause rhythmic contraction and expansion of the thoracic cavity.

- (2) movement of the respiratory muscles

muscles:
intercostal muscles, and the primary expiratory muscles are internal intercostal muscles as well as abdominal muscles.

- the inspiratory muscles mainly include the diaphragm and external

quiet breathing
- Inspiration movement: contraction of the diaphragma and external

intercostal muscles increase diameter of the thorax.

- Expiration movement: the diaphragma and external intercostal muscles relax, the thorax recover by elasticity.

forced breathing
- Inspiration movement: contracted by diaphragma and external intercostal muscles and assistant inspiratory muscle. - Expiration movement: contracted by internal intercostal muscle and assistant expiratory muscle.

process:
bottom of the pleural cavity downward, thus elongating it. Second, the external intercostals and neck muscles lift the front of the thoracic cage, causing the ribs to angulate more directly forward than previously, increasing the thickness of the cage.

- Inspiratory process: First, contraction of the diaphragm pulls the

- Expiratory process: First, abdominal muscles and intercostal

muscles pull downward on the thoracic cage, thereby decreasing

the thoracic thickness. Second, they force the abdominal contents upward, thus pushing the diaphragm upward as well and thereby decreasing the longitudinal dimension of the pleural cavity. The internal intercostals pull the ribs downward. When ribs are in this downward position, the thickness of the chest is considerably decreased.

(3) types
- thoracic breathing: breathing caused primarily by the movement of external intercostal muscles. - abdominal breathing: normal quiet breathing is accomplished almost entirely by movement of the diaphragm, it is called ~.

Inspiration and expiration

- Inspiration: mainly for the abdominal breathing, the lung volume

increase, anyone should recall from the basic laws of physics that
when a volume of gas is suddenly increased, its pressure falls. So that will cause intrapulmonary pressure less than atmospheric

pressure, then air will flow into the lungs. That is ~.

- Expiration: adverse process of inspiration, the lung volume decrease will cause intrapulmonary pressure more than atmospheric pressure, then air will flow out of the lungs.

3intrapulmonary pressure
- (1) concept: the pressure of air inside the lung alveoli.
(2) principle: respiratory movement

intrapulmonary pressure the pressure difference

up and down alternately with periodism

between intrapulmonary pressure and air pressure changed with

periodism proportional

the air moves into and out of the lungs

4intrapleural pressure (Pip)

- (1) concept
pleural sac: an airtight larvate cavity between the visceral pleura and parietal
pleura.

pleural pressure: the pressure in the pleural sac.

(2) mechanism
- airtightness of the pleural sac
There are only some intrapleural fluid in the airtight pleural sac, the visceral
pleura and parietal pleura attached together tightly and form a larvate cavity, draw the lung to move with the thorax movement.

Any change in the volume of the thorax is immediately reflected by a similar

change in the volume of the lungs.

- expanded lung has elastic recoil

The intrinsic volume of the lung far less than that of the thorax. When a man
grew, the growth velocity of the thorax was faster than that of the lung, so the lung always in the stretched state, and has retracted tendency.

the negative pleural pressure

pleural cavity: intrapulmonary pressure that keeps the alveoli expanded and the recoil pressure of the lungs that causes the alveoli to collapse.

- Formation of ~ depends on two kinds of forces that act on the

- Pleural pressure= intrapulmonary pressure - the recoil pressure of the lung

At end of inspiration or expiration, intrapulmonary pressure is the same as air
pressure (supposed to be zero), so Pleural pressure= - the recoil pressure of the lung. About -5mmHg. But that is a relative value. In fact, the really true absolute value is about 755mmHg (760mmHg - 5mmHg).

(3) normal value

- Quiet breathing: at the end of the inspiration -10~ -5mmHg; at the end of the expiration -5~ -3mmHg

(4) physiology significance

- to make the alveoli keep the expanding state for maintaining normal lung ventilation - facilitates return of venous blood and lymph to the heart because it is helpful for expansion of the vena cava and pectoral duct in thoracic cavity

(5) pneumothorax
- When an opening wound is made in the chest wall the elastic forces in the lungs cause them to collapse immediately, sucking air through the opening into the chest cavity. This is called a ~.

Then, when the person tries to breathe, instead of the lungs expanding and contracting, air flows in and out of the hole in the chest. Thus, a wound of the chest can kill a person by suffocation; yet the condition can be treated by sucking air out of the pleural cavity and plugging the hole.

Air flow in the pleura, so intrapleural pressure will not be negative, but be equal to atmospheric pressure. Then lung will collapse because of the elastic recoil.

The resistance of lung ventilation

1 elastic resistance and compliance

Elastic resistance: the ability of an elastic structure to resist stretching of
distortion.

Compliance: the expandability of the elastic tissue under the external force
effect. It is often defined as the magnitude of the change in lung volume produced by a given change in the transpulmonary pressure.

It is obviously that compliance is inversely proportional to elastic resistance,

that is, the larger the compliance, the less elastic resistance.

- (1) Elastic resistance and compliance of the lung

 The elastic resistance of expanded lung is composed of elastic

recoil, and is measured by compliance. - Lung compliance = Change in lung volume / change in transpulmonary pressure

CL

VL

static compliance curve of the lung

- The slope of the pressure-volume reflects changes of the lung

compliance or elastic resistance relative to altered volume of the lung.

When quiet breathing, the lung compliance is approximately 0.2L/cmH2O, and is situated in the biggest part of slope in the curve. So, the elastic resistance is small and person breathes easily at this time.

specific compliance of the lung

elastic resistance of individuals.

- It is the compliance per unit volume and is used to compare the lung

the source of elastic resistance of the lung

- 1/3 elastic recoil of the lungs

2/3 surface tension at the air-water interfaces within the alveoli

pulmonary surfactant

- Produced and secreted by the type alveolar cells.

Component: a complex mixture of several phospholipids.

- Its main components are the DPPC (dipalmitoyl phosphatidyl choline) and SP (surfactant-associated protein).

Functions:
- To maintain the stability of the alveoli (to make all alveoli

expand, make big and small alveoli all expand);

According

to the law of laplace, P=2T/r

- P: pressure, T: surface tension, r: radius of alveolus

What is Surface Tension ?

Within Fluid All forces balance

At surface Unbalanced forces Generate Tension

Surface Tension

Law of Laplace:
- Pressure in alveoli is directly proportional to surface tension; and inversely proportional to radius of alveoli. - Pressure in smaller alveolus would be greater than in larger alveolus, if surface tension were the same in both.

Effect of Surface Tension on Alveoli size

Air Flow Expand Collapse

Surfactant prevents alveolar collapse

Area dependence of Surfactant action

Low S/unit Area

Saline
Slider - Change Surface Area Saline Increase Area Decrease Area
High S/unit Area

Area

Surfactant

Tension

So, the radius of the alveolus decrease, the pressure increase. Then the air in small radius alveolus will flow

into the big radius alveolus, and the small alveoli would be
unstable and would collapse into big alveoli, and big alveoli would be too big even blast.

But , the radius of the alveolus decrease , the density of the surfactant increase (because surface area decrease), thus reducing surface tension. Vice versa.

Then, the surfactant can prevent small alveoli to collapse,

and prevent big alveoli to blast.

- To reduce the sucking effect of surface tension on the interstitial fluid, to prevent pneumonedema and keep normal thickness of respiratory membrane; - To reduce lung elastic resistance and work of breathing.

(2) the elastic resistance and compliance of the thorax

- During the breathing process, the elastic resistance of the thorax is double direction, it can be resistance of the inspiration, as well as be that of the expiration (in deep breathing).

2Nonelastic resistance
- Airway resistance: account for 80%~90% of the total nonelastic resistance; it is caused by friction among gas molecules and between gas molecules and the inner wall of airway. - Inertial resistance: it is caused by inertial of gas and tissue when the gas is moving, shifting, changing direction. It can be ignored when quiet breathing. - Viscous resistance: it is caused by friction of tissue relative displacement. It is very small too.
fairway resistance ptranspulmonary pressure vvolumes of air flow in unit time

 Airway resistance is affected by gas speed, gas flow form and airway

radii.
- Gas speed more quick, the resistance more big.

There are two forms: laminar flow resistance is small and turbulent

flow resistance is big.

Airway resistance is inversely proportional to the fourth power of the

airway radii.

1r

Airway radii is affected by 4 factors:

- (1) transpulmonary pressure: in fact, it is trans-airway pressure. The
pressure in airway increase transpulmonary pressure increase airway radii increase passively resistance decrease, vice versa.

(2) That holds the airway open is the elastic connective tissue fibers linking the outside of the airway to the surrounding alveolar tissue. It is called lateral traction.

(3) Autonomic nervous system regulate the activity of airway smooth muscle. Sympathetic impulse act to relax the airway

smooth muscle, while parasympathetic activity causes

contraction of the muscle.

(4) Chemical factors: some endocrine and paracrine factor, for example, catecholamine (CA) relax the airway smooth muscle and decrease the airway resistance, histamine contract the

muscle and increase the resistance.

Pulmonary volumes and pulmonary ventilation

Mostly, there are some important concepts:

1pulmonary volumes
- (1) tidal volume (TV): the volume of air inspired or expired in each normal breath, is approximately 500ml. - (2) inspiratory reserve volume (IRV): the maximum extra volume of air the can be inspired over and above the TV. - (3) expiratory reserve volume (ERV): the maximum extra volume of air that can be expired by forceful expiration after the end of the TV. - (4) residual volume (RV): the volume of air still remains in the lungs that can NOT be expired after the end of the forceful expiration .

2pulmonary capacities
- (1) inspiratory capacity (IC): IC=TV+IRV. - (2) function residual capacity (FRC): the volume of air that still remains in the lungs after expiration of a resting tidal volume. The physiologic significanPo2s to prPco2nt great fluctuations of and in the alveoli and therefore in arterial blood during breathing. - (3) vital capacity (VC): the maximal volume of air that a person can expire after a maximal inspiration.
VC= IRV+TV+ERV
- Everyone has different VC due to differences in figure, sex, age, body position, and the force of the respiratory muscles.

- (4) total lung capacity (TLC): the maximum volume of air the lung can accommodate.

3pulmonary ventilation
- It is the total amount of air inspired or expired each minute.

pulmonary ventilation=TV respiratory rate

4dead space
- (1) anatomic dead space
Much of the air pulled into the respiratory passages with each breath never
reaches the alveoli because it merely fills the passageways such as the nose, the

pharynx, the trachea, and the bronchi. Then this air is expired without ever
entering the alveoli. This air is useless from the point of view of oxygenating the blood. So the respiratory passageways are called ~. The total volume of this space is normally about 150ml, which means that during inspiration of a

normal tidal volume of 500ml, only 350ml of new air actually enters the alveoli.

- (2) alveolar dead space

Some inspired fresh air is not used for gas exchange with the blood even though
it reaches the alveoli because some alveoli have little or no blood supply for some reasons. So this volume of air is termed ~.

- (3) physiologic dead space

The sum of the anatomic and alveolar dead space.

5alveolar ventilation
- The most important measure of the effectiveness of a persons respiration is his alveolar ventilation rate, which is the total quantity of new air that enters his alveoli each minute.
- Alveolar ventilation=(TV-dead space) respiratory rate

6work of breathing

The work that respiratory muscles perform to cause pulmonary ventilation in the process of breathing.

It can be calculated by changes in transmural pressure

multiply changes in the lung volume.

It is used to conquer elastic and non-elastic resistance of

lungs and chest wall.

Exchange of gases

1gas diffusion
(1) some concepts

Partial pressure: the individual gas pressure in mixed gas total pressure.
Gas diffusion principle: gas molecules always transfer from high partial pressure place to low partial pressure place.

Diffusion rate (D): the volume of gas diffusion in unit time.

(2) formula

P T A S d MW

D is diffusion rate, P is the pressure difference between the two ends of the diffusion pathway, T is the temperature, A is the diffusion area of the pathway, S is the solubility of the gas, d is the distance of diffusion, and MW is the molecular weight of the gas.

The power of the gas diffusion is the difference of the partial pressure. So net diffusion of a gas occurs from a region where its partial pressure is high to a region where

it is low.

2the partial pressure of different position in body

Factors that affect the gas exchange

1the thickness of the respiratory membrane

- The respiratory membrane consists of the six different layers: (1) a layer of fluid lining the alveolus and containing surfactant that reduce the surface tension of the alveoli. (2) the alveoli epithelium. (3) an epithelial basement membrane. (4) a thin interstitial space between the alveoli epithelium and the capillary membrane. (5) a capillary basement membrane. (6) the capillary endothelial

membrane.
- But all thickness of the membrane only about 0.6 micrometer, some

area even only 0.2 micrometer. So it is easy for gas diffusion.

If the thickness of the membrane increase for some reasons (disease), that mean the distance of diffusion increase, then diffusion rate will fall, gas exchange speed will be slow,

2the surface area of the membrane

- The diffusion rate is in proportion to the diffusion area. - In resting state, the area is about 40m2; in moving state, the area is about 70m2 because more pulmonary capillary is open.

3ventilation / perfusion ratio

- The ratio between alveolar ventilation (mL/min, VA) and pulmonary blood flow (mL/min, Q). The normal value of VA/ Q in a healthy adult

average 0.84. The adequate gas exchange is achieved only with

adequate VA/ Q. Any mismatching between ventilation and perfusion is termed ventilation-perfusion inequality. - VA/ Q increase: means ventilation is excessive or blood flow is not enough, part of alveolar gas did not exchange with pulmonary capillary blood. So it is equal to dead space increase. Often occurred in upper lung.

VA/ Q decrease: means the ventilation is not enough or blood flow is excessive, part of blood supply the alveoli which are short of ventilation. Then the gas in venous

blood cant renew enough, like functional arterio-venous

shunt. Often occurred in the bottom of the lung.

The main effect of ventilation-perfusion inequality is to decrease the PO2 of systemic arterial blood.

Gas transport
1basic information The gas transport is a bridge that connect external respiration to internal respiration. Transport forms of O2 and CO2: main form is chemical combination, minor form is physical dissolution, but physical dissolution is the precondition of chemical combination.

2transport of oxygen (1) transport forms and amount

Dissolved in the plasma and erythrocyte; Combined with hemoglobin molecules in the erythrocyte. The amount of oxygen dissolved in blood is about 1.5% at the normal

arteria PO2 of 100mmHg. 98.5% of the oxygen is transported in the erythrocytes reversibly combined with hemoglobin. O2 in the form of chemical combination is called oxyhemoglobin (HbO2) .
Hemoglobin is a very important effective carrier for oxygen transport

because of its structure of its molecules.

A single hemoglobin molecule can bind four molecules of oxygen. The

reaction of oxygen with hemoglobin is oxygenation but not oxidation.

(2) some concepts:

Oxygen capacity: In 100ml blood sample, the maximal capacity of hemoglobin to bind oxygen. Oxygen content: In 100ml blood sample, the actual binding amount of oxygen with hemoglobin. Oxygen saturation: O2 bound to hemoglobin divided by the maximal capacity of hemoglobin to bind O2.

Cyanosis: A bluish discoloration of the skin and mucous membranes resulting from inadequate oxygenation of the blood when deoxyhemoglobin in blood reaches to 5g/100ml. It also can be observed in lip and finger nail.

3transport of carbon dioxide in the blood (1) transport forms and amount

5% CO2 remains physically dissolved in the plasma and erythrocytes. 95% CO2 in the blood is combined with chemical substances, mainly in the forms of bicarbonate (88%) and carbamino hemoglobin (7%).

(2) bicarbonate

Most of the CO2 molecules enter the erythrocytes from the blood in

the tissues and react with water to form bicarbonate. The reversible
reaction of CO2 with H2O to form carbonic acid is very slow unless catalyzed by the carbonic anhydrase.

(3) carbamino hemoglobin

A part of CO2 molecules that enter the blood react reversibly with the

amino groups of hemoglobin to form carbamino hemoglobin. This reaction goes rapidly without enzyme assistance.

(4) movement of CO2

Regulation of respiration
Respiratory center and respiratory rhythm

1respiratory center (1) the role of spinal cord There exit motor neurons that innervate the respiratory muscles;

It is a relay station that receives signals from the brain and then sends impulses to the respiratory muscles;

It works as an elementary center that is involved in some respiratory reflexes.

confirmed by the animal experiments were made by transection of the brain stem at various levels. Medulla oblongata:

The generating site of the basic respiratory rhythm.

Most of inspiratory neurons lie in several nuclei of the medulla, they are called medullary inspiratory neurons. Especially in DRG (dorsal group of respiratory neurons) and VRG (ventral group of respiratory neurons). Pons:

An important area of the lower pons called the apneustic center, that is the major source of the synaptic input which

1st layer: between the midbrain and pons.(no change)

2nd layer: between the upper and middle pons. (apneusis )

3rd layer: between the pons and medulla.(gasping)

4th layer: between the medulla and spinal cord.

(3) higher level brain

Respiratory movement is also controlled by signals from
higher centers such as the cerebral cortex and diencephalons, which can control the voluntary breathing.

Mainly regulate the conditional reflex.

2generation of respiratory rhythm

(1) the pacemaker theory

The pacemaker-like neurons in the medulla cause respiratory rhythm like the pacemakers in the heart that produce rhythmic cardiac activity. But it has not been confirmed that whether these neurons are present in adult

It is thought that the formation of respiratory rhythm is dependent on interactions between the respiratory neurons, which are in complex contact. Many models have been proposed based on a lot of experiments. Among them, the

most famous model is the central inspiratory activity

generator and inspiratory off-switch mechanism model.

PBKF: NPBM (medial parabrachial necleus ) plus Kolliker-Fuse (KF), where respiratory neurons are densely distributed.

PBKF
(+) (+) ( )

Central inspiratory generator Inspiratory neurons

(+)

(+)

Switch-off mechanism
(+) vagi

Inspiratory motor neurons

(+)

Inspiration

Inspiratory movement expansion of lung stretch receptor(+)

Reflex control of breathing

1pulmonary stretch reflex (1)Concept: inflation of the lungs caused inhibition of inspiration, while collaps of the lungs enhanced inspiration. This reflex is called .

Pulmonary inflation reflex: the process of suppressed

inspiration by inflation of the lungs.

Pulmonary deflation reflex: the reflex in which deflation of the lungs enhances inspiration.

(2) process

 Afferent

nerve: vagi

Nerve center: medullary Efferent nerve: phrenic nerve and intercostal nerves Effector: respiratory muscle

The pulmonary stretch reflex has difference in varies animals. The most obvious reflex can be observed on
rabbits. In human, this reflex plays a unimportant role in setting respiratory rhythm unless under conditions of very

large tidal volumes.

2chemical control of breathing (1) chemoreceptor and its afferent nerve

They are located high in the neck at the bifurcation of the common carotid arteries and on the arch

of the aorta in the thorax.

They are stimulated mainly by decrease in arterial PO2 and increase in the arterial H+ concentration.

The afferent nerve of carotid

body is sinus nerve; the afferent

nerve of aortic body is vagi.

central chemoreceptors

They are located in the medulla and, like the peripheral

chemoreceptors, provide excitory synaptic input to the medullar inspiratory neurons.

They are stimulated by an increase in the H+ concentration of the brains extracellular fluid, that is cerebrospinal fluid. The changes of H+ concentration result mainly from changes in blood PCO2.

(2) control respiratory by CO2O2H+

CO2

Cross BBB

Pco2 in CSF

CO2+H2O

CA

H2CO3

Pco2 in blood sti Sinus nerve vagi + Medullary respiratory center

HCO3 sti Central chemoreceptor

Peripheral chemoreceptor

H+

Motor neuron of respiratory muscle in spinal cord + phrenic nerve intercostal nerves

Diaphragma and external intercostal muscles contract Respiratory movement deepen and quicken

 A certain

level of PCO2 in the blood is necessary to maintain

the respiratory center active. If PCO2 were lowered to a critical point, breathing would cease.

But , high concentrations of CO2 act directly on the medulla to inhibit the respiratory neurons by an

anesthesia-like effect. Other symptoms caused by very high

blood PCO2 include severe headache, restlessness, and dulling or loss of consciousness.

H+ (not due to altered CO2)

Increased H+ in the arterial blood can cause enhanced

pulmonary ventilation, vice versa.

pass through the blood-brain barrier.

In the contrast, CO2 rapidly passes through the BBB (for

good liposolubility) and changes brain H+ concentration. Central chemoreceptor is sensitive to H+ concentration

changes of the brains extracellular fluid.

O2

On the one hand, decrease of PO2 can stimulate peripheral chemoreceptors then excite the respiratory center; on the

other hand, decrease of PO2 can act directly on the medulla

to inhibit the respiratory movement. So the effect on respiratory by decrease of PO2 lies on degree of low PO2.

 interaction of effects on respiratory by CO2, O2, and H+ (pH, power of hydrogen) The decrease of O2 and pH can enhance the excitation of respiratory by increase of CO2. In fact, three factors often change at the same time, interact each other.