FUNCTIONAL ANATOMYMECHANICS OF RESPIRATION

Rodolfo T. Rafael,MD., DPAFP

PHYSIOLOGY OF RESPIRATION

Exchange and Transport of Respiratory Gases

Respiratory Exchange Ratio

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Rodolfo T. Rafael,M.D., DPAFP

PHYSIOLOGY OF RESPIRATION• Regulation of Respiration

Rodolfo T. Rafael, M.D., DPAFP

Structure and Function of the Respiratory System

gas exchange host defense metabolic organ

LUNG ANATOMY

contained in a space 4L- surface area for gas exchange (∼85 m2)

demonstrate functional unity- similar to kidney

Weight 1 kg 60% tissue

Alveolar spaces lung volume interstitium- collagen, potential space for

fluid and cells to accumulate

Upper Airways-Nose, Sinuses, Larynx

Nose---> distal alveolus nasal cavity, posterior pharynx,

glottis, vocal cords, trachea, tracheobronchial tree.

Upper airway nose -------- > vocal cords

Lower airways trachea ------- > alveoli

Upper Airways

condition inspired air nose

filter entrap, clear particles > 10μm, and provides the sense of smell

20ml surface area increase

by the nasal turbinates

Upper Airways

10,000 to 15,000 L/day Nasal resistance

50% nose 8cm H2O/L/sec viral infections, exercise high mouth breathing

Interior of the nose - respiratory epithelium-surface secretory cells immunoglobulins, inflammatory mediators,

and interferons.

Upper Airways

The paranasal sinuses (frontal sinuses, maxillary sinus, sphenoid sinus, ethmoid sinus) ciliated epithelium ?

The sinuses have two major functions- they lighten the skull they offer resonance to the voice.

They may also protect the brain during frontal trauma.

In some sinuses (e.g., the maxillary sinus), the opening (ostium) is at the upper edge- retention of mucus.

Sinusitis-obstructed ostia nasal edema retention of secretions

Upper Airways The major structures of the larynx include the

epiglottis arytenoids vocal cords

infectionsedematous airflow resistance. The epiglottis and arytenoids "hood" or cover

the vocal cords during swallowing.

The act of swallowing food after mastication (chewing) usually occurs within 2 seconds, and it is closely synchronized with muscle reflexes that coordinate opening and closing of the airway.

Lower Airways-Trachea, Bronchi, Bronchioles, Respiratory Unit

The right lung, located in the right hemithorax divided into three lobes (upper,

middle, and lower) by two interlobular fissures (oblique, horizontal)

Left lung, located in the left hemithorax is divided into two lobes (upper,

including the lingula, and lower) by an oblique fissure

Lower Airways

Visceral pleura Parietal pleura

The interface of these two pleuras allows for smooth gliding of the lung as it expands in the chest and produces a potential space.

Air – pneumothorax Fluid- pleural effusion empyema

Lower Airways

The trachea bifurcates (branches) into two main stem bronchi main stem bronchi lobar bronchi (one

for each lobe) segmental bronchi bronchioles alveolus

Lower Airways

lung supplied by a segmental bronchus - functional anatomic unit of the lung.

Bronchi and bronchioles differ size cartilage type of epithelium blood supply

dichotomous or asymmetric branching pattern- terminal bronchioles

respiratory bronchioles results in decreased diameter * the total surface area for that generation increases in size and number until the respiratory bronchiole terminates in an opening to a group of alveoli

Lower Airways

The alveoli polygonal in shape and about 250 μm in

diameter. 5 × 108 alveoli Type I and type II epithelial cells

1:1 ratio.

The type I cell occupies 96% to 98% of the surface area

of the alveolus the primary site for gas exchange. the basement membrane of type I cells

and the capillary endothelium are fused The type II epithelial cell

small and cuboidal and is usually found in the "corners" of the alveolus

occupies 2% to 4% of its surface area synthesize pulmonary surfactant

Lower Airways Alveolar-capillary network

Gas exchange occurs 1 to 2 μm in thickness type I alveolar epithelial cells, capillary endothelial

cells, and basement membranes. < 1 second

Injury and type I cell deaththe type II cell replicates and differentiates into type I cells to restore normal alveolar architecture

Phylogeny recapitulating ontogeny- embryonic development the

epithelium of the alveolus- composed of type II cells

Lung Interstitium Composed of connective tissue, smooth muscle,

lymphatics, capillaries, and a variety of other cells.

Fibroblasts are prominent cells in the interstitium of the lung collagen and elastin Collagen is the major structural component of the

lung that limits lung distensibility. Elastin is the major contributor to elastic recoil of the

lung. Cartilage Kultschitzky cells- neuroendocrine cells- biogenic

amines- fetus- bronchial carcinoid

BLOOD SUPPLY TO THE LUNG-PULMONARY AND BRONCHIAL CIRCULATIONS

The lung has two separate blood supplies. The pulmonary circulation

deoxygenated blood- right ventricle to the gas-exchanging units for removal of CO2 and oxygenation.

The bronchial circulation arises from the aorta- nourishment to the

lung parenchyma.

Pulmonary Circulation

The pulmonary capillary bed largest in the body surface area of 70 to

80 m2

The network of capillaries is so dense that it might be considered to be a sheet of blood interrupted by small vertical supporting posts

Pulmonary Circulation The capillary volume in the lung at rest is

70 mL. During exercise- volume increases

200 mL. Increase?

The pulmonary veins return blood to the left atrium - supernumerary

conventional branches provide a large reservoir for blood, and they can either

increase or decrease their capacitance to provide constant left ventricular output in the face of variable pulmonary arterial flow.

Pulmonary arteries and veins with diameters larger than 50 μm contain smooth muscle.

Bronchial Circulation

The bronchial arteries three in number provide a source

of oxygenated, systemic blood to the lungs

accompany the bronchial tree and divide with it

Bronchial Circulation bronchi, bronchioles, blood vessels, and nerves perfuse the lymph nodes and visceral pleura. 1/3 of the blood returns to the right atrium-

bronchial veins 2/3 drains into the left atrium- pulmonary veins.

Cystic fibrosis, the bronchial arteries, which normally receive only 1% to 2% of cardiac output, increase in size (hypertrophy) and receive as much as 10% to 20% of cardiac output.

The erosion of inflamed tissue into these vessels secondary to bacterial infection- hemoptysis

INNERVATION Breathing is automatic - central nervous

system (CNS). The peripheral nervous system (PNS) includes

both sensory and motor components. conveys and integrates signals from the

environment to the CNS. Sensory and motor neurons of the PNS transmit

signals from the periphery to the CNS. Somatic motor neurons- skeletal muscles Autonomic neurons- smooth muscle, cardiac

muscle, and glands. The lung- autonomic nervous system of the

PNS, which is under CNS control

INNERVATION There are four distinct components of the

autonomic nervous system: parasympathetic (constriction) sympathetic (relaxation) nonadrenergic noncholinergic inhibitory

(relaxation) nonadrenergic noncholinergic stimulatory

(constriction). (+) parasympathetic system leads to airway

constriction, blood vessel dilation, and increased glandular secretion.

(+) sympathetic system causes airway relaxation, blood vessel constriction, and inhibition of glandular secretion

INNERVATION

As with most organ systems, the CNS and PNS work in cohort to maintain homeostasis.

Lungs no voluntary motor no pain fibers

Pain fibers

INNERVATION The parasympathetic innervation - medulla in

the brainstem (cranial nerve X, the vagus). Preganglionic fibers - vagal nuclei

vagus nerve ganglia adjacent to airways and blood vessels in the lung.

Postganglionic fibers – ganglia smooth muscle cells, blood vessels, and bronchial epithelial cells (including goblet cells and submucosal glands).

Both preganglionic and postganglionic fibers contain excitatory (cholinergic) and inhibitory (nonadrenergic) motor neurons. Acetylcholine and substance P dynorphin and vasoactive intestinal peptide

INNERVATION Parasympathetic

(+) vagus nerve--> slight constriction of smooth muscle tone in the normal resting lung.

bronchial glands--> increase the synthesis of mucus glycoprotein, raises the viscosity of mucus.

greater larger airways, and it diminishes toward the smaller conducting airways in the periphery.

Response of the parasympathetic nervous system very specific and local

Response of the sympathetic nervous system more general.

INNERVATION

Sympathetic Nervous System Mucous glands and blood vessels

mucous glands increases water secretion.

Upsets the balanced response of increased water and increased viscosity between the sympathetic and parasympathetic pathways

Central Control of Respiration Breathing is an automatic, rhythmic, and

centrally regulated process with voluntary control.

brainstem- main control center for respiration Regulation of respiration requires

generation and maintenance of a respiratory rhythm

modulation of this rhythm by sensory feedback loops and reflexes that allow adaptation to various conditions while minimizing energy costs

recruitment of respiratory muscles that can contract appropriately for gas exchange.

MUSCLES OF RESPIRATION-DIAPHRAGM, EXTERNAL INTERCOSTALS, SCALENE

The major muscles of respiration include the diaphragm the external intercostals scalene

Skeletal muscles provide the driving force for ventilation the force of contraction increases when they are

stretched and decreases when they shorten. The force of contraction of respiratory muscles

increases at larger lung volumes. The process of respiration or gas exchange begins

with the act of inspiration, which is initiated by contraction of the diaphragm.

Diaphragm Contraction

protrudes into the abdominal cavity decrease chest pressure inspiration

Relaxation exhalation increase chest pressure

Major muscle of respiration Divides the thoracic cavity from the abdominal

cavity airway pressure= 150-200 cmH2O Quiet breathing- 1 cm Deep-Breathing= 10 cm R and L phrenic nerves

FLUIDS LINE THE LUNG EPITHELIUM AND PLAY IMPORTANT PHYSIOLOGICAL ROLES

The respiratory system is lined with three fluids: periciliary fluid mucus surfactant

Periciliary fluid and mucus components of the mucociliary clearance system and line the

epithelium of the conducting airways from the trachea to the terminal bronchioles.

they form the basis for the mucociliary clearance system, which aids in the removal of particulates (e.g., bacteria, viruses, toxins) from the lung

Surfactant lines the epithelium of the alveolus and provides an "antistick"

function that decreases surface tension in the alveolus

Cells of the Mucociliary Clearance System

The respiratory tract to the level of the bronchioles is lined by a pseudostratified, ciliated columnar epithelium maintain the level of periciliary fluid

5-μm layer of water and electrolytes in which cilia and the mucociliary transport system function.

depth is maintained by the movement of various ions- chloride secretion and sodium absorption

Mucus and inhaled particles - rhythmic beating of the cilia on the top of the pseudostratified, columnar epithelium. Each epithelial cell contains about 250 cilia.

Cells Regulating Mucus Production Goblet or surface secretory cells

produce mucus increase in number in response to chronic cigarette smoke

(and environmental pollutants) increased mucus and airway obstruction in smokers.

Submucosal tracheobronchial glands * cartilage in the tracheobronchial tree. empty to the surface epithelium through a ciliated duct,

and they are lined by mucus-secreting mucous and serous cells

increase in number and size in chronic bronchitis, and they extend down to the level of the bronchioles in pulmonary disease.

Clara cells are found at the level of the bronchioles- the goblet cells and submucosal glands have disappeared. granules with nonmucinous material and may have a

secretory function. play a role in epithelial regeneration after injury.

Surfactant and Surface Tension The alveoli are lined with surfactant. Surface tension

force caused by water molecules at the air-liquid interface that tends to minimize surface area, thereby making it more difficult to inflate the lung.

The effect of surface tension on lung inflation is illustrated by comparing the volume-pressure curves of a saline-filled versus an air-filled lung.

Higher pressure is required to fully inflate the lung with air than with saline because of the higher surface tension forces in air-filled versus saline-filled lungs.

Surfactant and Surface Tension Surface tension is a measure of the attractive

force of the surface molecules per unit length of material to which they are attached.

The units of surface tension are those of a force applied per unit length.

For a sphere (such as an alveolus), the relationship between the pressure within the sphere (Ps) and the tension in the wall is described by the law of Laplace:

Surfactant and Surface Tension In the absence of surfactant

the surface tension at the air-liquid interface would remain constant and the transmural (transalveolar) pressure needed to keep it at that volume would be greater at lower lung (alveolar) volumes

Thus, greater transmural pressure would be required to produce a given increase in alveolar volume at lower lung volumes than at higher lung volumes.

Surfactant stabilizes the inflation of alveoli because it allows the surface tension to decrease as the alveoli become larger As a result, the transmural pressure required to keep an

alveolus inflated increases as lung volume (and transpulmonary pressure) increases, and it decreases as lung volume decreases.

Surfactant and Surface Tension “Interdependence”

Alveoli surrounded by other alveoli. The tendency of one alveolus to collapse is

opposed by the traction exerted by the surrounding alveoli. collapse of a single alveolus stretches and distorts

the surrounding alveoli, which in turn are connected to other alveoli.

pores of Kohn canals of Lambert

The pores of Kohn and the canals of Lambert provide collateral ventilation and prevent alveolar collapse (atelectasis).

Composition and Function of Surfactant

phospholipids, neutral lipids, fatty acids, and proteins. 85% to 90% lipids, predominantly phospholipids, 10% to

15% proteins. The major phospholipid- phosphatidylcholine, 75% of

dipalmitoyl phosphatidylcholine (DPPC). major surface-active component in surfactant.

2nd phosphatidylglycerol (PG)1% to 10% of total surfactant. important in the spreading of surfactant over a large surface area.

Surfactant is secreted by type II cells Cholesterol and cholesterol esters account for the majority

of the neutral lipids; their precise functional role is not yet fully understood, but they may aid in stabilizing the lipid structure.

Composition and Function of Surfactant

Four specific surfactant proteins (SP-A, SP-B, SP-C, SP-D) make up 2% to 5% of the weight of surfactant

SP-A most studied which is expressed in alveolar type II cells and in Clara cells in the lung. involved in the regulation of surfactant turnover, in immune regulation

within the lung, and in the formation of tubular myelin. Two hydrophobic surfactant-specific proteins are SP-B and SP-C. SP-B

involved in tubular myelin formation and the surface activity (i.e., surface tension, spreading ability) of surfactant, and it may increase the intermolecular and intramolecular order of the phospholipid bilayer.

SP-C involved in the spreading ability and surface tension activity of surfactant.

The function of SP-D is unknown at this time.

Composition and Function of Surfactant

Secretion of surfactant via exocytosis of the lamellar body . β-adrenergic agonists, activators of protein kinase C,

leukotrienes, and purinergic agonists The major routes of clearance of pulmonary surfactant

within the lung are reuptake by type II cells, absorption into the lymphatics, clearance by alveolar macrophages

Pulmonary surfactant serves several physiological roles, including (1) reducing the work of breathing by decreasing surface

tension forces (2) preventing collapse and sticking of alveoli on expiration (3) stabilizing alveoli, especially those that tend to deflate at

low surface tension.

THE LYMPHATIC SYSTEM

Major functions of the lymphatic network in the lung Host defense removal of lymph fluid from the lung

The lymphatic capillaries are highly specialized to allow the transfer of fluid from the interstitial spaces into the lymphatic capillaries.

Although the lymphatic capillaries are somewhat similar to blood capillaries, they have several distinct features that aid in fluid movement and clearance: (1) there are no tight junctions between endothelial cells (2) fine filaments anchor the lymph vessels to adjacent

connective tissue such that with each muscle contraction the endothelial junctions open to allow fluid movement

(3) valves enhance lymph flow in one direction.

STATIC LUNG MECHANICS

Lung Volumes

Total lung capacity (TLC), the total volume of air that can be contained in the lung. Lung volumes are reported in liters either as volumes or as capacities.

Lung Volumes

(tidal volume [VT]) that is moved with each quiet breath is measured.

Lung Volumes

Vital capacity (VC)- The total volume of exhaled air, from a maximal inspiration to a maximal exhalation

Residual volume (RV) is the air remaining in the lung after a complete exhalation. Functional residual capacity (FRC) is the volume of air in the lung at the end of exhalation during quiet breathing and is also called the resting volume of the lung. FRC is composed of RV and the expiratory reserve volume (ERV; the volume of air that can be exhaled from FRC to RV).

Lung Volumes

The ratio of RV to TLC (RV/TLC ratio) is used to distinguish different types of pulmonary disease. In normal individuals, this ratio is usually less than 0.25. An elevated RV/TLC ratio, secondary to an increase in RV out

of proportion to any increase in TLC, is seen in diseases associated with airway obstruction, known as obstructive pulmonary diseases.

An elevated RV/TLC ratio can also be caused by a decrease in TLC, which occurs in individuals with restrictive lung diseases.

Determinants of Lung Volume What determines the volume of air in

the lung at TLC or at RV? The answer lies in the properties of the

lung parenchyma and in the interaction between the lungs and the chest wall.

The lungs and chest wall always move together in healthy individuals.

Measurement of Lung Volumes RV and TLC can be measured in two

ways: helium dilution body plethysmography.

Both are used clinically and provide valuable information about lung function and lung disease.

Lung Compliance (CL)

is a measure of the elastic properties of the lung. It is a measure of how easily the lung is

distended. is defined as the change in lung volume resulting

from a 1-cm H2O change in the distending pressure of the lung.

The units of compliance are mL (or L)/cm H2O. High lung compliance refers to a lung that is

readily distended. Low lung compliance, or a "stiff" lung, is a lung

that is not easily distended.

Pressure-Volume Relationships Air flows into and out of the airways from areas of higher

pressure to areas of lower pressure. In the absence of a pressure gradient, there is no airflow. Minute ventilation is the volume of gas that is moved

per unit of time. It is equal to the volume of gas moved with each breath

times the number of breaths per minute:

VE= VT X fwhere VE is minute ventilation in mL or L/min, VT is tidal volume in mL or L, and f is the frequency or number of breaths per minute.

DYNAMIC LUNG MECHANICS

Airflow in Airways

Air flows through the airways when there is a pressure difference at the two ends of the airway.

During inspiration, the diaphragm contracts, pleural pressure becomes more negative (relative to atmospheric pressure), and gas flows into the lung (from the higher to the lower pressure).

Gas exchange to meet the changing metabolic needs of the body depends on the speed at which fresh gas is brought to the alveoli and the rapidity with which the metabolic products of respiration (i.e., CO2) are removed.

Two major factors determine the speed at which gas flows into the airways for a given pressure change: the pattern of gas flow resistance to airflow by the airways

Airflow in Airways

There are two major patterns of gas flow in the airways-laminar and turbulent flow. Laminar flow is parallel to the airway

walls and is present at low flow rates. As the flow rate increases and particularly

as the airways divide, the flow stream becomes unsteady and small swirls occur.

At higher flow rates, the flow stream is disorganized and turbulence occurs.

French physician Poiseuille

Airway Resistance

Airflow resistance is the second major factor that determines rates of airflow in the airways.

Airflow resistance in the airways (Raw) differs in airways of different size.

In moving from the trachea toward the alveolus, individual airways become smaller while the number of airway branches increases dramatically.

Raw is equal to the sum of the resistance of each of these airways (i.e., Raw = Rlarge + Rmedium + Rsmall). The major site of resistance along the bronchial tree is the

large bronchi. The smallest airways contribute very little to the overall

total resistance of the bronchial tree

In a normal lung, most of the resistance to airflow occurs in the first eight airway generations

Factors That Contribute to Airway Resistance

In healthy individuals, airway resistance is approximately 1 cm H2O/L · sec.

One of the most important factors affecting resistance is lung volume. Increasing lung volume increases the caliber of the airways. resistance to airflow decreases with increasing lung volume, and it

increases with decreasing lung volume.

Airway mucus, edema, and contraction of bronchial smooth muscle, all of which decrease the caliber of the airways.

The density and viscosity of the inspired gas also affect airway resistance. Breathing a low-density gas such as an oxygen-helium mixture

results in a decrease in airway resistance

Neurohumoral Regulation of Airway Resistance

Stimulation of efferent vagal fibers, either directly or reflexively, increases airway resistance and decreases anatomic dead space

secondary to airway constriction (recall that the vagus nerve innervates airway smooth muscle).

Stimulation of the sympathetic nerves and release of the postganglionic neurotransmitter norepinephrine inhibit airway constriction.

Reflex stimulation of the vagus nerve by the inhalation of smoke, dust, cold air, or other irritants result in airway constriction and coughing.

Agents such as histamine, acetylcholine, thromboxane A2, prostaglandin F2, and leukotrienes (LTB4, LTC4, and LTD4) are released by resident (e.g., mast cells and airway epithelial cells) and recruited (e.g., neutrophils and eosinophils) airway cells in response to various triggers, such as allergens and viral infections. act directly on airway smooth muscle to cause constriction and an

increase in airway resistance. Inhalation of methacholine, a derivative of acetylcholine

used to diagnose airway hyperresponsiveness, which is one of the cardinal features of asthma.

The Spirogram

A spirogram displays the volume of gas exhaled against time

four major test results: (1) forced vital capacity (FVC) (2) forced expiratory volume in 1

second (FEV1) (3) the ratio of FEV1 to FVC

(FEV1/FVC) (4) the average midmaximal

expiratory flow (FEF25-75).

Flow-Volume Loop

A newer way of measuring lung function clinically is the flow-volume curve or loop.

A flow-volume curve or loop is created by displaying the instantaneous flow rate during a forced maneuver as a function of the volume of gas.

This instantaneous flow rate can be displayed both during exhalation (expiratory flow-volume curve) and during inspiration (inspiratory flow-volume curve)

END

Quiz1. Contraction of diaphragm create______ pressure inside the chest.2. Relaxation of diaphragm create______ pressure inside the chest.3. ____________ the total volume of air that can be contained in the lung.

Lung volumes are reported in liters either as volumes or as capacities. 4. _________________ The total volume of exhaled air, from a maximal

inspiration to a maximal exhalation5. __________________is the air remaining in the lung after a complete

exhalation. 6. ____________________is the volume of air in the lung at the end of

exhalation during quiet breathing and is also called the resting volume of the lung.

7. The ratio of ____________________ is used to distinguish different types of pulmonary disease.

8. During inspiration, the diaphragm _____________, pleural pressure becomes more __________ (relative to atmospheric pressure), and gas flows into the lung.

9. ______ an instrument displays the volume of gas exhaled against time 10. Function of the respiratory system