Respiration Physiology

陳雅雯 助理教授

ext. 2177

Vander’s Human PhysiologyThe Mechanisms of Body Function

References

Review of Medical PhysiologyGanong

Vander, sherman, & Luciano’s

Organization of the respiratory system

• Pulmonary: lung

• Alveolus: tiny air-containing sac, the site of gas exchange with blood, 300 million/adult.

• Airway: the tubes that air flows through from the external environment to the alveolus.

• Inspiration (inhalation), Expiration (exhalation).

• Respiratory cycle: Inspiration Expiration.

Respiratory cycle

Housing the vocal cords

Inspiration air

The walls of trachea and bronchus contain rings of cartilage, which give them their cyclindrical shape and support them.

Airways

no cartilage

alveolus appear

no alveolus and no gas exchange with the blood

Figure 34-1. Structure of the lung. A, alveolus; AD, alveolar duct; RB, respiratory bronchiole; TB, terminal bronchiole. (Modified from Staub NC: The pathophysiology of pulmonary edema. Hum Pathol 1970;1:419.)

Alveolus

Alveolar wall

Contain interstitial fluid and connective tissues

The Lung: Scientific Foundations Second Edition 423-545, 1997

Type II cells of alveolar epithelium:

1. The site of production and secretion of pulmonary surfactant.

2. Production of new cells in repair after injury.

3. During normal tissue turnover. Int J EXP Pathol 78: 291-310, 1997

The Lung: Scientific Foundations Second Edition 423-545, 1997

Lamellar body

Figure 34-13. Formation and metabolism of surfactant. Lamellar bodies (LB) are formed in type II alveolar epithelial cells and secreted by exocytosis. The released lamellar body material is converted to tubular myelin (TM), and the TM is probably the source of the phospholipid surface film (SF). Some surfactant is taken up by alveolar macrophages, but more is taken up by endocytosis in type II epithelial cells. N, nucleus; RER, rough endoplasmic reticulum; CB, composite body. (Reproduced, with permission, from Wright JR: Metabolism and turnover of lung surfactant. Am Rev Respir Dis 1987;136:426.)

(75 m2)

Components of thoracic wall: spinal column, ribs, sternum ,intercostal muscles and connective tissue.

Bronchus

Lung

Pleural sac

(intrapleural pressure, Pip)

Ventilation and lung mechanics

Bulk flow

F (flow)

= P (pressure)

R (resistance)

= (Palv-Patm)

R (resistance)

Alveolar pressure (Palv)

Atmospheric pressure (Patm)

Boyle’s law

Lung volume depends on (1)transpulmonary pressure (Ptp)-between the inside and the outside of the lungs, (2)how stretchable the lungs are.

Rest: Palv=0, Patm=0, Pip= - 4 mmHg

How is a stable balance achieved between breaths .

Elastic recoil: the tendency of an elastic structure to oppose stretching or distortion.

(Rest)

Normal inspiration at restPhrenic nerves: diaphragm

Interscostals nerves: inspiratory intercostals muscles

Normal expiration at rest

Lung compliance

There are two major determinants of lung compliance:

(1)Elastic connective tissues lung tissues

thickening compliance

(2) Surfactant surface tension

compliance

Interactive Respiratory Physiology

In fibrosis the lungs become stiff, making a large pressure necessary to maintain a moderate volume. Such lungs would be considered poorly compliant.

Lung fibrosis

Emphysema

Compliance of the lung in emphysema is significantly above normal; the lung becomes easy to distend but empties slowly.

Interactive Respiratory Physiology

Laplace law

Respiratory distress syndrome (RDS)

Newborn

(The lung filled with amniotic fluid)

Maternal blood

oxygen

Surfactant synthesizing cells immature

Low lung compliance

Respiratory distress syndrome (RDS) of the newborn

Premature infants.

The surfactant synthesizing cells may be

immature to function adequately.

Complete exhaustion, inability to breath,

lung collapse, death.

Therapy: mechanical ventilator, natural or

synthetic surfactant.

Airway resistance

F= (Palv-Patm)/R

Physical factors

Neural factors

Chemical factors

Airway radii

Airway resistance

Transpulmonary pressure

Elastic connective tissues fiber

Physical factorsTranspulmonary pressure (Ptp)

1.which exerts a distending force on the

airway.

2.inspiration: Ptp, airway radius, airway

resistance, lung expand.Elastic connective tissues fiber

1. which link the outside of the airways to the

surrounding alveolar tissue.

2. lateral traction: which pull the airway open.

Neural factors

Neuroendocrine and paracrine factors:

Epinephrine

leukotrienes(-adrenergic

receptors)(members of eicosanoid family)

(airway smooth muscle)

Relaxation

Contraction

Forced expiratory volume in 1s (FEV1)

The person takes a maximal inspiration and then exhales maximally as fast as possible.

The important value is the fraction of the total forced vital capacity expired in 1s.

The normal individuals can expired approximately 80% of the vital capacity in 1s.

Obstructive lung disease

Airway resistance

A FEV1 that is less than 80% of the vital

capacity.

It is difficult to expire air rapidly through

the narrowed airway.

Restrictive lung disease

Normal airway resistance but impaired respiratory movement because of abnormalities in the lung tissue, the pleura, the chest wall, or the neuromuscular machinery.

A normal ratio of FEV1 to vital capacity.

Reduction of vital capacity.

Ventialtion

Minute ventialtion (VE)

Minute ventialtion = Tidal volume x Respiratory rate(ml/min)

(ml/breath)

(breaths/min)

(VE

)

(Vt) (f)

6000 ml/min = 500 ml/breath x 12 breath/min

Alveolar ventialtion (VA)

Alveolar ventilation (ml/mln)

Tidal volume

(ml/breath)

Dead space

(ml/breath)

Respiratory rate

(breaths/min)

= - x

(VA

)

(Vt) (f)(VD

)

4200 ml/min = (500 ml/breath – 150 ml/breath)

x 12 breaths/min

Dead space

Anatomic dead space: conducting airway, these airway do not permit gas exchange with the blood.

Alveolar dead space: some fresh inspired air is not used for gas exchange with blood even though it reachs the alveoli.

Physiologic dead space: the sum of anatomic dead space and alveolar dead space.This is as known as “wasted” ventilation.

Exchange of gases in alveoli and tissues

Oxygen

Alveolar membrane

Pulmonary capillaries

Blood

Tissues

Tissue capillaries

Extracellular fluid

Plasma membranes

Cells

Carbon dioxide

The steps of gases exchange in alveoli and tissues

Respiratory quotient (RQ)

The ratio of CO2 produced to O2 consumed.

For example, on a mixed diet, the RQ is approximately 0.8; that is, 8 molecules of CO2 are produced for every 10 molecules of O2 consumed,

RQ

Carbohydrate:1

Fat:0.7

Protein:0.8

(O2 consumption/min)

(CO2 production/min)

(21%x4L/min)

Partial pressure of gases As Dalton’s law states, in a mixture of

gases, the pressure each gas exert is independent of the pressure the other exert.

The individual pressures, termed partial pressure (P).

Partial pressure of oxygen: PO2

Partial pressure of carbon dioxide: PCO2

Net diffusion of a gas: high to low

Diffusion of gases in liquid Henry’s law states that the amount of gas

dissolved will be directly propotional to the partial pressure of the gas with which the liquid is in equilibrium.

PO2 of Gas phase> PO2

of liquid phase O2 dissolved in water

water

O2

Balance:

gas phase PO2 = liquid phase PO2

(alveolar)

(capillary)

Alveolar gas pressure

The factors that determine the precise value

of alveolar PO2 are

(1) the PO2 of atomospheric air,

(2) the rate of alveolar ventilation,

(3) the rate of total body oxygen conusmption.

The factors that determine the precise value

of alveolar PCO2 are

(1) the rate of alveolar ventilation,

(2) the rate of total body oxygen conusmption.

The relationship of alveolar ventilation and partial pressure

Net diffusion: two sides of the alveolar-capillary membrane

Lung infection Lung edema Diffuse interstitial fibrosis

Ventilation-perfusion inequality

Alveolar air flow (ventilation) and capillary blood flow (perfusion) mismatching.

The major effect is lower PO2 of the

systemic arterial blood.

Gravity effect: to increase the filling of blood vessels at the bottom of the lung.

Disease states: change in (1) Lung compliance, (2) airway resistance, (3) vascular resistance

No perfusion

No ventilation

Ventilation-perfusion inequality

PO2 , PCO2

Local control of ventilation-perfusion matching

Transport of oxygen in blood

Normal arterial PO2 100

mmHg

Hemoglobin = 4 Heme

Heme = 1 polypeptide+1 Fe2+

4 polypeptide= globin

O2 +Hb HbO2

deoxyhemoglobin

oxyhemoglobin

Heme

Percent hemoglobin (Hb) saturation

O2 bound to Hb

Maximal capacity of Hb to bind O2

X 100

=

Oxygen-carrying capacity of blood

The factors determined the percent hemoglobin saturation are PO2

and the amount of Hb.

What is the effect of PO2 on

hemoglobin saturation ?

Oxygen-hemoglobin dissociation curveThe law of mass action:

Blood PO2 oxygen-Hb combination

Effect of added hemoglobin on oxygen distribution

The oxygen bound to Hb dose not contribute directly to the PO2

of the blood; only dissolved oxygen does so.

Oxygen movement in the lung

PO2=40 mmHg

PO2=105

mmHg

Plasma PO2

oxygenerythrocyte

erythrocyte PO2

HbO2 formation

Oxygen movement in the tissues

Carbon monoxide

colorless, odorless gas

A product of incomplete combustion of hydrocarbons, such as gasoline.

It is about 200 times of high affinity for the oxygen binding sites in hemoglobin.

oxygen combined with Hb in lung capillary.

Shift the oxygen-hemoglobin dissociation curve to left.

unloading of oxygen from Hb in the tissues.

Factors influence the degree of hemoglobin saturation

Blood PO2

Blood PCO2

H+ concentration

Temperature

2,3-diphosphoglycerate (DPG), [also as

known as 2,3-Bisphosphoglycerate (BPG)]

Hb has less affinity for oxygen

Hb has greater affinity for oxygen

Transport of carbondioxide (cell to blood)

Dissolved

Interstitial fluid

Dissolved

Dissolved

10%

30%

60%

(Carbonic anhydrase)

Chloride shift

Total blood carbon dioxide

The sum of

(1) Dissolved carbon dioxide (plasma and RBC)

(2) Bicarbonate (HCO3-)

(3) Carbon dioxide in carbamino hemoglobin

(HbCO2)

Transport of carbondioxide (blood to alveolus)

Transport of hydrogen ions between tissues and lungs

Hyperventilation and hypoventilation

Hyperventialtionrespiratory alkalosis:

arterial (1) PCO2 (2) H+

Hypoventialtionrespiratory acidosis:

arterial (1) PCO2 (2) H+

Nitric oxide (NO)

Lung

Blood

HbO2 HbNO

Peripheral tissues

Hb+O2 Hb+NO

NO:

(1) Vasodilator agent

(2) A treatment for persistent pulmonary hypertension in new born children

Control of respiration

Neural generation of rhythmical breathing

Pons

Medulla oblongata

Pneumotaxic center

Apneustic center

Respiratory rhythm generator Medullary inspiratory neurons

Synchronic discharge

Cease discharge

Inspiration Expiration

LungPulmonary strec

h receptors

(Hering-Breuer reflex)

Control of ventilation by PO2

, PCO2, and H+

concentration

Peripheral chemoreceptors

Peripheral chemoreceptors provide excitatory synaptic input to the medullary inspiratory neurons.

(Under the PCO2=40 mmHg

condition)

The effect on ventilation of breathing low-oxygen mixtures.

Control by PO2

Low arterial PO2 causes

hyperventilation

Control by PCO2 Inspiration of

PCO2

Alveolar PCO2

Arterial PCO2

Ventilation

Ex: a defect of respiratory system (emphysema)

Pathways by which increased arterials PCO2 stimulates

ventilation.

Control by [H+]

Respiratory acidosis: ventilation PCO2

[H+]

Respiratory alkalosis: ventilation PCO2

[H+]

Metabolic acidosis: [H+]

Metabolic alkalosis: [H+]

Elimination of PCO2

effect

The peripheral chemoreceptors play the major role in altering ventilation.

Control by non-PCO2 but enhance by

[H+]Strenuous exercise

Lactic acid accumulation

Peripheral chemoreceptors

Hyperventilation

Central chemoreceptors: less effect of [H+], because H+ penetrate the blood-brain barrier very slowly.

Control by non-PCO2

but enhance by [H+]

Summary of the major chemicals inputs that stimulate ventilation.

The effect of exercise on ventilation, arterial gas pressure and hydrogen ion

concentration.

Hyperventilation in strenuous exercise

Lactic acid accumulation

The roles of other factors stimulate ventilation Reflex input from mechanoreceptors in joints and muscles

Body temperature

Inputs to the respiratory neurons via branches form axons descending from the brain to motor neurons supplying the excising muscles

In the plasma epinephrine concentration

In the plasma potassium concentration

A conditioned (learned) response mediated by neural input to the respiratory centers.

Ventilation changes during exercise

Other ventilatory responses

Protective reflexes: cough and sneeze reflexes

Voluntary control of breathing

Reflexs from J receptors: J receptors exist in the capillary wall or the interstitium

Hypoxia: a deficiency of oxygen at tissue level

Hypoxic hypoxia (hypoxemia) arterial PO2

Anemic or carbonmonoxide hypoxia inadequate numbers of RBC

Ischemic hypoxia (hypoperfusion hypoxia) blood flow to the tissues is too low

Histotoxic hypoxia toxicant interfere the cell’s metabolic machinery

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