chap22 powerpoint

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Chapter 22The

RespiratorySystem

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Respiratory System

• Anatomy of the Respiratory System• Pulmonary Ventilation• Gas Exchange and Transport• Respiratory Disorders

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Anatomy of Respiratory System

• 3 general meanings:

1. Ventilation of lungs (breathing)2. Gas exchange between the air and blood and

between blood and tissue3. Use of O2 in cellular metabolism

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Anatomy of Respiratory SystemCommon function: provide gas exchangeOther possible functions:

• Serves for speech and other vocalization• Sense of smell• Eliminates CO2, controls pH of body fluids

– (CO2 + H20 → H2CO3 → HCO3- + H+), acidosis

• Lungs carry step in synthesis of a vasoconstrictor angiotensin II.

• Breathing creates pressure gradients between the thorax and abdomen, which promotes flow of lymph & venous blood

• Valsalva maneuver (holding breath helps to expel abdominal contents during urination, defecation, birthing

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Principle organs:Nose, pharynx, larynx, trachea, bronchi, lungs

Organs of Respiratory System

Anatomy of Respiratory SystemRespiratory system is divided into 2 divisions:

1. Conducting division– passages that serve ONLY airflow, nostrils to bronchioles

2. Respiratory division– Consists of aveoli and other distal gas-exchange regions;

Upper respiratory tract– organs in head and neck, nose through larynx

Lower respiratory tract– organs of thorax, trachea through lungs

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Nose• Functions

– warms, cleanses, humidifies inhaled air;– detects odors;– resonating chamber that amplifies the voice;

Extends from the anterior (external) nares (nostrils) to a pair of posterior (internal) nares (choana);

Nosesuperior half: nasal bones medially and maxillae laterally;inferior half: lateral and alar cartilages;ala nasi: flared portion shaped by dense CT, forms lateral wall of each nostril;

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Nose (internal chamber of nose)

Nasal cavity (internal chamber) divided into right and left nasal fossae by nasal septum;

Nasal Cavity begins at the vestibule just inside the nostril- Lined with stratified squamous epithelium, vibrissae (guard hairs);

Vestibule contains 3 fold of tissue called:1. superior conchae2. middle conchae3. inferior conchae

Beneath each conchae is a narrow air passage called a meatus.

Function of conchae: - causes tubulence that ensures air comes into contact with the mucous membrane. Enables nose to cleanse, warm, & humidify air.

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Upper Respiratory Tract

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Upper Respiratory Tract

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NoseOlfactory mucosa (sensory cells)

- lines roof of nasal fossa

Respiratory mucosa (nonsensory), nasal cavity - lungs

2 Principle type of cells1. Goblet Cells (mucus production) trap inhaled particles;2. ciliated pseudostratified epithelium which lines rest of nasal

cavity (in lungs changes to ciliated cuboidal epi.);

Defensive role of mucosa, contains lysozyme that destroy bacteria;

Lamina propria is well populated with lymphyocytes for immune defense against inhaled pathogens.

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Nose• Function of cilia of respiratory epithelium

– sweep debris-laden mucus into pharynx to be swallowed;

• Inferior conchae contains erectile tissue (swell body)– venous plexus that rhythmically engorges with blood and

shifts flow of air from one side of fossa to the other once or twice an hour to prevent drying;

• Epistaxis (nosebleed)– Caused by trauma to lower nasal septum or insertion of

finger;– most common spontaneous site of a epistaxis is the

inferior concha. (possible early sign of hypertension)

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Pharynx

Divided into 3 regions

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PharynxNasopharynx (pseudostratified

epithelium)– posterior to choanae, dorsal to

soft palate;– receives auditory tubes and

contains pharyngeal tonsil;– 90 downward turn traps large

particles (>10m);

Oropharynx (stratified squamous epithelium)– space between soft palate and

root of tongue, inferiorly as far as hyoid bone, contains palatine and lingual tonsils;

Laryngopharynx (stratified squamous)

– hyoid bone to level of cricoid cartilage; esophagus begins at this point.

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Larynx (“voicebox”)

Primary function is to keep food an drink out of the airway. But it evolved the additional role of phonation (sound production)

in many animals & especially human.

Superior opening of larynx is guarded by the Epiglottis During swallowing extrinsic muscle of larynx pull the larynx upward toward the epiglottis, the tongue pushes the epiglottis down, which guides the food & drink into the esophagus;

Vestibular folds: play a bigger role in keeping food & drink out of the airway by close the glottis during swallowing

Infant larynx - higher in throat, forms a continuous airway from nasal cavity that allows breathing while swallowing;- by age 2, root of tongue becomes muscular, forces larynx to descend.

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Larynx (add) Epiglottic cartilage - most superior;Thyroid cartilage – largest anterior lateral aspect; laryngeal prominence

(“adam’s apple”);

Cricoid cartilage - connects larynx to trachea along with thyroid cartilage they constitute the “box” of the “voicebox”;

Arytenoid cartilages (2) & Corniculate cartilages (2) – function in speech;

Cuneiform cartilages (2) - support soft tissue between arytenoids and epiglottis

LarynxContains:Extrinsic ligaments: link the larynx to other organ;

- thyrohyoid ligament – joins thyroid cartilage to hyoid bone;

- cricotracheal ligament – joins cricoid cartilage to the trachea;

Intrinsic ligaments: internally link all 9 cartilages together.- 2 pairs

1. vestibular ligaments 2. Vocal ligaments

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Muscles of LarynxExtrinsic muscles (superfical): connect larynx to hyoid

bone, elevate larynx during swallowing. (aka infrahyoid group)

Intrinsic muscles (deep): operate the vocal cords.

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Walls of Larynx• Interior wall has 2 folds on each side:

– vestibular folds: superior pair, close glottis during swallowing;

– vocal cords (folds): inferior pair- produce sound when air passes through them; stratified squamous epithelium, well suited for vibration and contact between cords.

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LarynxIntrinsic muscles - rotate corniculate and arytenoid cartilages

causing the cartilage to pivot;

Adducted cords = tightens: high pitch soundAbducted cords = loosens: low pitch sound

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Trachea“Windpipe”, anterior to esophagus;

Supported by 16 to 20 “C”-shaped cartilaginous rings made of hyaline cartilage;- prevents the pipe from collapsing when inhale; allows room for expansion of esophagus when swallowing food;- opening in rings faces posteriorly towards esophagus;- trachealis muscle spans (posterior aspect) opening in rings,

Function: adjusts tracheal airflow by expanding or contracting;

Larynx and trachea lined with ciliated pseudostratified epitheliumwhich functions as mucociliary escalator – cilia drive debris-

laden mucus toward pharynx to be swallowed.

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Trachea

Trachea

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The trachea will divide at the inferior end into a right & left bronchi, the low most tracheal cartilage has an internal ridge called the carina;

- helps to direct air flow to the right or left.

Lungs & Bronchial TreeEach lung has an apex, base, costal surface,

mediastinal surface, and hilum (primary bronchus, blood vessels, lymphatic vessels, & nerves enter lung);

Right lung is shorter than the left due to liver;Left lung is narrower than the right due to the heart,

contains the cardiac impression;

Right lung has 3 lobes: Superior, middle, inferior;Left lung has 2 lobes: Superior, inferior

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Lungs - Surface Anatomy

Lungs & Bronchial TreeBronchial tree – highly branched system

2 primary bronchi branch from trachea at the angle of the sternum;

- Right bronchi is slightly wider and more vertical than the left (aspirated foreign objects more freq);

- Contain hyaline “C” shaped cartilage, important for expelling air from the lungs;

Upon entering the hilum the 1o bronchi become the 2o (lobar) bronchus for each lobe of the lung;

The 2o bronchus divides into 3o (segmental) bronchi, 10 in right lobe & 8 in left lobe.

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Lungs & Bronchial Tree3o bronchi Bronchioles terminal bronchioles

(final branches of the conducting division) respiratory bronchioles (beginning of respiratory division) divide into alveolar ducts which end in alveolar sacs.

1o bronchi 2o bronchi 3o bronchi bronchiolesterminal bronchioles respiratory bronchiolesalveolar ducts alveolar sacs

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AlveolarEach lung consists of 150 million little sacs, alveoli, where as the frog is a simple sac lined with blood vessels.

That’s a surface area 70m2 gas exchange at one time!

Equivalent to 230 sq. ft.

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Alveolus3 types of cells present in the alveolus (pouch):

1. Squamous (type I) alveolar cell2. Great (type II) alveolar cell3. Alveolar microphages

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Alveoli1. Squamous (type I) alveolar cells

• Cover 95% of the surface area• Thin – allow for rapid gas diffusion between alveolar and blood

stream.

2. Great (type II) cells• Cover 5% of the surface area, cuboidal shape• 2 functions:

1. Repair alveolar epithelium when type 1 are damaged2. Secrete Pulmonary Surfactant (prevents the alveoli from

collapsing when one exhales)

3. Alveolar macrophages (dust cells)• Most numerous• Phagocytize dust particles & other debris• 100 million of them die each day as they ride the mucociliary

escalator.

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Respiratory Membrane• Consists of:

1. Squamous alveolar cells2. Squamous endothelial cells3. Basement membrane (shared by both 1 & 2)

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Lung Tissue

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Pleurae• Visceral (on lungs) and parietal (lines rib cage)

pleurae;• Pleural cavity (potential space)- space between

pleurae, lubricated with pleural fluid;• Functions (plurae & fluid)

– reduce friction (pleurisy);

– create pressure gradient• lower pressure (pleural cavity) assists lung inflation;

– compartmentalization• prevents spread of infection.

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Pulmonary Ventilation• Breathing (pulmonary ventilation) – one cycle of

inspiration and expiration;– quiet respiration – at rest when not thinking about it;– forced respiration – deep or rapid breathing, during

exercise;

Fundamental fact about pulmonary ventilation - Flow of air in and out of lung requires a pressure difference between air pressure within lungs and outside body.

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Respiratory Muscles• Diaphragm (dome shaped)

– contraction flattens diaphragm• Scalenes - hold first pair of ribs stationary• External and internal intercostals

– stiffen thoracic cage; increases diameter • Pectoralis minor, sternocleidomastoid and

erector spinae muscles– used in forced inspiration

• Abdominals and latissimus dorsi– forced expiration (to sing, cough, sneeze)

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Respiratory Muscles

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Neural Control of BreathingHeart has internal pacemaker and continues beating

when nerves are cut.

Respiration does not have any of these features.

Breathing depends upon continuous brain stimulation;

Two reasons for this dependence on brain:1. Skeletal muscle, unlike cardiac, can not contract

without nervous stimulus,2. Breathing involves multiple muscle, and must be

coordinated by a central mechanism.

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Brainstem Respiratory CentersUnconscious cycle breathing is controlled by 3

respiratory centers in the medulla oblongata:

1. Dorsal respiratory group (DRG)

2. Ventral respiratory group (VRG)

3. Pneumotaxic Center

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Brainstem Respiratory Centers1. Dorsal Respiratory Group (DRG)

Neurons of this center are called Inspiratory (I) neurons (upper motor neurons), firing causes inspiration;

Fibers of phrenic nerve go to diaphragm; intercostal nerves to intercostal muscles;

- DRG input stops abruptly, inspiratory muscles relax, thoracic cage recoil allows for exhalation;

DRG begins firing again, 3 seconds later.

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Brainstem Respiratory Centers2. Ventral Respiratory Group (VRG)

• Contains (I) neurons, and Expiratory (E) neurons;• Active during inspiration and exhalation;• Little activity during quite respiration;• Comes into play in heavy breathing, ie exercise;• involved in forced expiration, by activating abdominal &

accessory muscles.

Pons3. Pneumotaxic Center

• Regulates the shift from inspiration to expiration,• Output inhibits DRG and terminates inspiration;• Strong output = each breath shorter, respiratory rate faster;• Weak output = long, slow breaths.

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Respiratory Control Centers

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Central & Peripheral Input to Respiratory Centers

Respiratory rhythym is not constant but varies from state to state, ie sleeping, emotional states;

Such adaptations are possible because the respiratory centers of the medulla and pons receive input from other levels of the NS

From limbic system and hypothalamus– Pain & emotions affect breathing– Gasping, crying, laughing, anxiety


Multiple sensory receptors also provide information to the respiratory center:

1. Central chemoreceptors2. Peripheral chemoreceptors3. Stretch receptors4. Irritant receptors

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1. Central Chemoreceptors:- Brainstem neurons that respond to changes in pH in the cerebral spinal fluid;

- pH of the CSF reflects the CO2 levels in the blood; by regulating respiration this can ensure a stable CO2 level.

2. Peripheral Chemoreceptors:- located in carotid & aortic bodies of lg arteries above heart;-respond to O2 & CO2 content & pH of blood;- carotid bodies communicate with brainstem via CN IX;- aortic bodies via CN X;- both sensory fibers synapse with the DRG. 22-47


3. Stretch Receptors:

- found in the smooth muscle of bronchi, bronchioles & visceral pleura;- respond to inflation of the lungs & signal DRG;- Excess inflation triggers the inflation (Hering-Breuer) reflex, which…

inhibits the inhibitory neurons (DRG) during extreme stretching of the lungs (protective somatic reflex).

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4. Irritant Receptors:

- nerve endings in the epithelial cells of the airway;- respond to smoke, dust, pollen, chemical fumes, cold air, excess mucous;

resulting in protective reflexes:

- bronchoconstriction- shallower breathing- breath-holding-coughing

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Peripheral Chemoreceptor Paths

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Voluntary Control

• Neural pathways– motor cortex of frontal lobe of cerebrum sends

impulses down corticospinal tracts to respiratory neurons in spinal cord, bypassing brainstem

• Limitations on voluntary control– blood CO2 and O2 limits cause automatic

respiration

Pressure & AirflowUnderstanding the ventilation of the lungs, transport of

gases in blood & exchanges of gases with tissues, we have to be familiar with the gas laws of physics;

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Pressure & AirflowRespiratory airflow is governed by the same principles

that govern blood flow;

The pressure that drives respiration is atmospheric (barometric) pressure – weight of air above us;

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Pressure & AirflowOne way to change the pressure of a gas is to

change the volume of the container (Boyle’s Law);

Lungs contain a quantity of gas and if lung volume increases, their internal pressure decreases; conversely…

Lung volume decreases; internal pressure increases.

Inverse relationship!

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Boyle’s Law

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Inverse relationship between P & VAs P ==> V

If Volume decreases ½ ==> Pressure increases 2X

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Pressure & AirflowIf intrapulmonary pressure drops lower than the atm.

pressure surrounding the body then air will flow …down its pressure gradient into the lungs;

If the intrapulmonary pressure rises above the atm. pressure, then air will flow…

out of the lungs;

To breath rhythmically all we have to do is raise and lower our lung pressure created by changes in volume thoracic cavity, by employing the neuromuscular mechanisms we just described.

Atm. Pressure = 760 mmHg

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Inhalation Exhalation(inspiration) (expiration)

-------------------------------------------------------Intra-alveolar(intra-pulm.) 758 mmHg 761 mmHgPressure (-2) (+1)------------------------------------------------------------------Intra-pleural Pressure 754 mmHg 757 mmHg

(-6) (-3)

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Inspiration - Pressure Changes intrapleural pressure

– as volume of thoracic cavity ,visceral pleura clings to parietal pleura

intrapulmonary pressure– lungs expand with visceral pleura

• Transpulmonary pressure– intrapleural minus intrapulmonary pressure (not all

pressure change in the pleural cavity is transferred to the lungs)

• Inflation aided by warming of inhaled air• 500 ml of air flows with a quiet breath

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Respiratory Cycle

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Passive Expiration

• During quiet breathing, expiration achieved by elasticity of lungs and thoracic cage

• As volume of thoracic cavity , intrapulmonary pressure and air is expelled

• After inspiration, phrenic nerves continue to stimulate diaphragm to produce a braking action to elastic recoil

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Forced Expiration

• Internal intercostal muscles – depress the ribs

• Contract abdominal muscles intra-abdominal pressure forces

diaphragm upward pressure on thoracic cavity

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Pneumothorax

• Presence of air in pleural cavity– loss of negative intrapleural pressure allows

lungs to recoil and collapse• Collapse of lung (or part of lung) is called

atelectasis

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Resistance to AirflowPressure is one determinant of airflow; the other

resistance;

3 factors:

1. Diameter of the bronchioles2. Pulmonary compliance3. Surface tension of the alveoli & distal bronchioles

Resistance to Airflow1. Diameter of the bronchioles

– Their ability to change size makes them the primary control over resistance to airflow;

– Bronchoconstriction (decrease diameter)• triggered by airborne irritants, cold air, parasympathetic

stimulation, histamine– Bronchodilation (increase diameter)

• sympathetic nerves, epinephrine increase airflow;

2. Pulmonary compliance– distensibility of lungs; change in lung volume relative to a change

intrapulmonary pressure– Compliance can be reduced by degenerative lung disease, lungs

become stiffen by scarring (TB, black lung disease)

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Resistance to Airflow3. Surface tension of the alveoli and distal bronchioles

Alveoli are relatively dry, but have a thin film of water over their epithelium;

Thin film of water needed for gas exchange– creates surface tension that acts to collapse alveoli and

distal bronchioles;

Pulmonary surfactant (great alveolar cells)

– decreases surface tension by disrupting the hydrogen bond of water;

Premature infants that lack surfactant suffer from respiratory distress syndrome.

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Alveolar VentilationNot all inhaled air is used in gas exchange.Dead air;

– fills conducting division of airway, cannot exchange gases so…

You can call the conducting division = Anatomic dead space

Some pulmonary diseases can decrease gas exchange in the alveoli due to lack of blood flow, fibrosis or edema;

Physiologic dead space– sum of anatomic dead space and any pathological alveolar

dead space.

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Alveolar Ventilation RateThis measurement is directly relevant to the bodies

ability to get O2 to tissue and dispose of CO2

Air that ventilates alveoli x respiratory rate

500mL, of this 150mL is dead air

350mL/breath x 12 breaths/min = 4200mL/min350mL/breath x 20 breaths/min = 7000mL/min

Alveoli never fully empty on expiration, typically there is about 1300mL that remain in alveoli = residual volume.

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Measurements of VentilationIt’s important to measure a person’s pulmonary ventilation in

order to assess the severity of a respiratory disease or monitor improvement or deterioration;

Spirometer - measures ventilation

This device records such variables as rate and depth of breathing, speed of expiration, and rate of oxygen consumption.

http://www.nlhep.org/testing2.htm

Measurements of VentilationRespiratory volumes

– tidal volume– inspiratory reserve volume (IRV)– expiratory reserve volume (ERV)– residual volume (RV)

Respiratory Capacities (by adding 2 or more respiratory volumes)

- vital capacity- inspiratory capacity-functional residual capacity-total lung capacity

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Measurements of Ventilation

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Respiratory Volumes and Capacities

Respiratory volumes & capacities are proportional to body size.

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Respiratory Volumes and Capacities

Age - lung compliance, respiratory muscles weaken;Exercise - maintains strength of respiratory muscles;

Body size - proportional, big body/large lungs;

Restrictive disorders pulmonary compliance (limiting lung inflation) thus

reducing vital capacity;– TB, Black lung disease (pulmonary fibrosis);

Obstructive disorders– interfere with airflow by narrowing or blocking airflow; hard

to exhale a given amount of air;– Asthma, emphysema, & chronic bronchitis

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Eupnea – characterized by relaxed, quiet breathing (tidal volume of 500mL and a respiratory rate of 12 -15 breaths per min.

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Composition of Air (add)

• Mixture of gases; each contributes its partial pressure– at sea level 1 atm. of pressure = 760 mmHg– nitrogen constitutes 78.6% of the atmosphere so

• PN2 = 78.6% x 760 mmHg = 597 mmHg

• PO2 = 20.9% 159

• PH2O = 0.5% 3.7

• PCO2 = 0.04% + 0.3

• PN2 + PO

2 + PH2O + PCO

2 = 760 mmHg

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Composition of Air

• Partial pressures (as well as solubility of gas)– determine rate of diffusion of each gas and gas

exchange between blood and alveolus• Alveolar air

– humidified, exchanges gases with blood, mixes with residual air

– contains: • PN

2 = 569

• PO2 = 104

• PH2O = 47

• PCO2 = 40 mmHg

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Alveolar Gas Exchange• Is the exchange of O2 and CO2 across the

respiratory membrane.

Air in the alveolus is in contact with a film of H2O and thus O2 must diffuse through it to get to the blood stream and CO2 must diffuse from the blood stream, through the water film to be exhaled.

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Alveolar Gas Exchange• Whenever air and H2O (air-water interface) are in

contact, gases diffuse down their concentration gradients, until the partial pressures of each gas in air is equal to partial pressure of water;

• Henry’s law– amount of gas that dissolves in water is determined by

its solubility in water and its partial pressure in air

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Alveolar Gas ExchangeThe greater PO2 in alveolar air, the more O2 the blood picks up;

Blood arriving at the alveolus has a higher PCO2 than air, it releases CO2 into the air;

Called unloading CO2 and loading O2 ; independent of each other;

The efficiency of this depends upon the RBC and the time it takes to reach equilibrium – 0.25 sec;

Alveolar Gas Exchange

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Some variables that affect the efficiency of alveolar gas exchange:

1. Pressure gradients of the gas;2. Solubility of the gases;3. Membrane thickness;4. Membrane area;5. Ventilation-perfusion coupling.

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Factors Affecting Gas Exchange1. Pressure gradients of the gases

– PO2 = 104 mm Hg in alveolar air versus 40mm Hg in blood

– PCO2 = 46 mmHg in blood arriving versus 40mm Hg in

alveolar air;

Factors Affecting Gas Exchange2. Solubility of gases

– CO2 20 times as soluble as O2

– O2 is 2x as soluble as N2

O2 has conc. gradient, CO2 has solubility

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Factors Affecting Gas Exchange3. Membrane thickness - only 0.5 m thick

- this thickness presents obstacles to diffusion;However,

- left ventricular failure can lead to a back up of pressure in the lungs & promotes capillary filtration into the CT resulting in thickening respiratory membrane = gases have farther to travel and can not keep pace with blood flow = blood with high PCO2

in blood and low PO2.

Factors Affecting Gas Exchange4. Membrane surface area – healthy lung has about 70m2

of respiratory membrane for gas exchange.- some disease process decrease the surface area thus decreasing gas exchange:

- emphysema, lung cancer, TB

5. Ventilation-perfusion coupling – gas exchange requires good ventilation of alveolus & good perfusion of its capillaries;

– the ability to match ventilation and perfusion to each other.

- If part of the lung is poorly ventilated because of tissue destruction, there is little point in having blood go there, so the body will shunt the blood to a part of the lungs that is well ventilated for gas exchange. 22-86

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Ventilation-Perfusion Coupling

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Ventilation-Perfusion Coupling

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• Most oxygen binds to hemoglobin to form oxyhemoglobin• Oxyhemoglobin releases oxygen in the regions of body cells• Much oxygen is still bound to hemoglobin in the venous blood

Oxygen Transport

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Oxygen TransportA. Oxygen

Hemoglobin – bound = 98.5%

Hb + O2 <===> HbO2

(reduced Hb) (oxyhemoglobin)

Oxygen dissolved in plasma = 1.5%

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Oxyhemoglobin Dissociation Curve

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Carbon Dioxide Transport 1. dissolved in plasma2. combined with hemoglobin3. in the form of bicarbonate ions

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Carbon Dioxide TransportCarbon dioxide

- carried in blood in several forms:

A. Dissolved in plasma: ~ 7%

B. Combines with globin part of Hb: 23%- called carbaminohemoglobinCO2 + Hb <===> Hb CO2

C. Most transported as bicarbonate ions:70%

CO2 + H2O <==> H2CO3 <==> H+ + HCO3-

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Systemic Gas Exchange

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Alveolar Gas Exchange Revisited

• Reactions are reverse of systemic gas exchange

• CO2 unloading– as Hb loads O2 its affinity for H+ decreases, H+

dissociates from Hb and bind with HCO3-

• CO2 + H2O H2CO3 HCO3- + H+

– reverse chloride shift• HCO3

- diffuses back into RBC in exchange

for Cl-, free CO2 generated diffuses into alveolus to be exhaled

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Alveolar Gas Exchange

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Factors Affect O2 Unloading

• Active tissues need oxygen!– ambient PO

2: active tissue has PO

2 ; O2 is released

– temperature: active tissue has temp; O2 is released

– Bohr effect: active tissue has CO2, which lowers pH (muscle burn); O2 is released

– bisphosphoglycerate (BPG): RBC’s produce BPG which binds to Hb; O2 is released body temp (fever), TH, GH, testosterone, and

epinephrine all raise BPG and cause O2 unloading ( metabolic rate requires oxygen)

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Oxygen Dissociation and Temperature

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Oxygen Dissociation and pH

Bohr effect: release of O2 in response to low pH

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• Haldane effect– low level of HbO2 (as in active tissue) enables

blood to transport more CO2

– HbO2 does not bind CO2 as well as deoxyhemoglobin (HHb)

– HHb binds more H+ than HbO2

• as H+ is removed this shifts the CO2 + H2O HCO3

- + H+

reaction to the right

Factors Affecting CO2 Loading

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Blood Chemistry and Respiratory Rhythm

• Rate and depth of breathing adjusted to maintain levels of:– pH– PCO

2

– PO2

• Let’s look at their effects on respiration:

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Effects of Hydrogen Ions

• pH of CSF (most powerful respiratory stimulus)• Respiratory acidosis (pH < 7.35) caused by

failure of pulmonary ventilation– hypercapnia: PCO

2 > 43 mmHg

• CO2 easily crosses blood-brain barrier• in CSF the CO2 reacts with water and releases H+

• central chemoreceptors strongly stimulate inspiratory center

– “blowing off ” CO2 pushes reaction to the left CO2 (expired) + H2O H2CO3 HCO3

- + H+

– so hyperventilation reduces H+ (reduces acid)

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Effects of Hydrogen Ions

• Respiratory alkalosis (pH > 7.45)– hypocapnia: PCO

2 < 37 mmHg

– Hypoventilation ( CO2), pushes reaction to the right CO2 + H2O H2CO3 HCO3

- + H+

H+ (increases acid), lowers pH to normal• pH imbalances can have metabolic causes

– uncontrolled diabetes mellitus• fat oxidation causes ketoacidosis, may be

compensated for by Kussmaul respiration(deep rapid breathing)

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Effects of Carbon Dioxide

• Indirect effects on respiration– through pH as seen previously

• Direct effects CO2 may directly stimulate peripheral

chemoreceptors and trigger ventilation more quickly than central chemoreceptors

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Effects of Oxygen

• Usually little effect• Chronic hypoxemia, PO

2 < 60 mmHg,

can significantly stimulate ventilation– emphysema, pneumonia– high altitudes after several days

Chloride Shift

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• bicarbonate ions diffuse out RBCs• chloride ions from plasma diffuse into RBCs• electrical balance is maintained

Chloride Shift

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CO2 (from tissues) diffuses into cap.:CO2 + H2O <=> H2CO3 <=> H+ + HCO3-

HCO3- leaves RBC ---> plasmaCl- moves into RBC to replace bicarbonate ion

When blood reaches lungs, all reactions are reversed:

Cl- moves out of RBC;

HCO3- moves into RBC;

H2CO3 forms <=> CO2 + H2O

CO2 diffuses into alveoli

Respiratory DisordersHypoxia – deficiency of oxygen in tissue or the inability

to use oxygen;Not a respiratory disease but a consequence of a disease;

Classified:Hypoxic hypoxia – state of low PO2 - usually due to

inadequate pulmonary gas exchange- high altitudes, drowning, aspiration, respiratory arrest,

degenerative lung diseases, CO poisoning;

Ischemic hypoxia – inadequate circulation of blood (CHF);Anemic hypoxia – is due to anemia, inability of the blood to

carry adequate oxygen;Histotoxic hypoxia – metabolic poisioning, cyanide prevents tissures

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HypoxiaSigns: cyanosis - blueness of skin;

Primary effect: tissue necrosis, organs with high metabolic demands affected first (brain, heart, kidneys);

Oxygen Toxicity – when pure O2 is breathed;

- generated hydrogen peroxide & free radicals that destroy enzymes & nervous tissue;

Leads to: seizures, coma & death.

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Chronic Obstructive Pulmonary DiseaseAny disorder in which there is a long term obstruction

of airflow and a substantial reduction in ventilation.

Asthma– allergen triggers histamine release;– intense bronchoconstriction (blocks air flow) & sometimes

suffocation;

Other COPD’s usually associated with smoking/air pollution or occupational airborne irritants:– chronic bronchitis – emphysema

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Chronic Obstructive Pulmonary DiseaseBeginning smokers experience inflammation & hyperplasia of bronchial

mucosa;

Chronic bronchitis – cilia immobilized and in number;– goblet cells enlarge and produce excess mucus;– sputum formed (mucus and cellular debris);

• ideal growth media for bacteria

– Smoking incapacitates alveolar macrophages thus leads to chronic infection and bronchial inflammation;

– Smokers develop chronic infections, bronchial inflammation w/ symptoms of dyspnea, hypoxia, cyanosis, attacks of coughing.

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Chronic Obstructive Pulmonary DiseaseEmphysema

– alveolar walls break down• much less respiratory membrane for gas exchange

– healthy lungs are like a sponge; in emphysema, lungs are more like a rigid balloon

– lungs fibrotic and less elastic– Inhale adaquately but the air passages collapse

• obstruct outflow of air• air trapped in lungs results in “barral chested” appearance. - This over stretched thoracic rib cagemusculature weakly contract = difficultyexhaling.

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Effects of COPD

pulmonary compliance and vital capacity• Hypoxemia, hypercapnia, respiratory

acidosis– hypoxemia stimulates erythropoietin release

and leads to polycythemia • cor pulmonale

– hypertrophy and potential failure of right side of heart due to obstruction of pulmonary circulation

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Smoking and Lung Cancer• Lung cancer accounts for more deaths than

any other form of cancer;– most important cause is smoking (15 carcinogens;)– Followed by air pollution;

3 Types of lung cancers:

1. Squamous-cell carcinoma2. Adenocarcinoma3. Small-cell (oat-cell) carcinoma

Smoking and Lung Cancer1. Squamous-cell carcinoma (most common)

– begins with transformation of bronchial epithelium ciliated pseudostratified columnar into stratified squamous;

– dividing cells invade bronchial wall, cause bleeding lesions;

– dense swirls of keratin appear replace functional respiratory tissue.

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Smoking and Lung Cancer2. Adenocarcinoma

– originates in mucous glands of lamina propria– Least common

3. Small-cell (oat cell) carcinoma– most dangerous; looks like oat clusters;– originates in primary bronchi, invades

mediastinum, metastasizes quickly.

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Progression of Lung Cancer

• 90% originate in primary bronchi• Tumor invades bronchial wall, grows around it,

compresses airway; may cause atelectasis• Often first sign of trouble is coughing up blood• Metastasis is rapid & usually occurs by time it is

diagnosed, – common sites: pericardium, heart, bones, liver, lymph

nodes and brain• Once metastasized prognosis is poor after diagnosis

– only 7% of patients survive for 5 years after diagnosis.

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Healthy Lung/Smokers Lung- Carcinoma

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