Chapter 22 Respiratory System

Respiration
ventilation of lungs exchange of gases between
air and blood blood and tissue fluid

use of O2 in cellular metabolism

Organs of Respiratory System

Nose, pharynx, larynx, trachea, bronchi, lungs

General Aspects of Respiratory System

Airflow in lungs
bronchi bronchioles alveoli

Conducting division/zone
passages serve only for airflow, nostrils/mouth to terminal bronchioles

Respiratory division
Respiratory bronchioles alveolar ducts and sacs alveoli

Upper respiratory tract

organs in head and neck, nose through larynx

Lower respiratory tract

organs of the thorax, trachea through lungs

Nose
Functions
warms, cleanses, humidifies inhaled air detects odors resonating chamber that modifies the voice

Bony and cartilaginous supports (fig. 22.2)

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

Anatomy of Nasal Region

Nasal Cavity
Animation: http://www.youtube.com/watch?v=FUa12oXwYZY Extends from nostrils to choanae (posterior naris)
ethmoid and sphenoid bones compose the roof palate forms the floor

Vestibule: dilated chamber inside ala nasi

stratified squamous epithelium, vibrissae (guard hairs)

Nasal septum divides cavity into right and left chambers called nasal fossae
inferior part formed by vomer superior part by perpendicular plate of ethmoid bone anterior part by septal cartilage

Upper Respiratory Tract

Upper Respiratory Tract

Nasal Cavity - Conchae and Meatuses

Superior, middle and inferior nasal conchae
3 folds of tissue on lateral wall of nasal fossa mucous membranes supported by thin scroll-like turbinate bones

Meatuses
narrow air passage beneath each conchae narrowness and turbulence ensures air contacts mucous membranes

Nasal Cavity - Mucosa

Olfactory mucosa lines roof of nasal fossa Respiratory mucosa lines rest of nasal cavity with ciliated pseudostratified epithelium Defensive role of mucosa
mucus (from goblet cells) traps inhaled particles lysozyme eliminates bacteria

Nasal Cavity - Cilia and Erectile Tissue

Function of cilia of respiratory epithelium
drive debris-laden mucus into pharynx to be swallowed

Erectile tissue of inferior concha

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)
most common site is the inferior concha

Regions of Pharynx

Pharynx
Nasopharynx (pseudostratified epithelium)
posterior to choanae, dorsal to soft palate receives auditory tubes and contains pharyngeal tonsil air turns 90 downward trapping 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 epithelium)

hyoid bone to cricoid cartilage (inferior end of larynx)

Types of epithelia
vestibule is lined by the protective stratified squamous epithelium, because the vestibule is a cavity that opens to the outside (and needs protections). oropharynx and laryngopharynx are ducts that are shared with the digestive system, so there is a need to provide protection from abrasion with a stratified squamous epithelium. nasopharynx receives air from the nasal cavity and is not close to the outside nor is it shared with the digestive system. The nasopharynx has the same epithelium as the nasal cavity: pseudostratified ciliated columnar.

Larynx
Glottis - superior opening Epiglottis - flap of tissue that guards glottis, directs food and drink to esophagus Infant larynx
higher in throat, forms a continuous airway from nasal cavity that allows breathing while swallowing by age 2, more muscular tongue, forces larynx down

Views of Larynx

Anterior

Posterior

Midsagittal

Nine Cartilages of Larynx

Epiglottic cartilage Thyroid cartilage - largest, has laryngeal
prominence

Cricoid cartilage - connects larynx to trachea Arytenoid cartilages (2) - posterior to thyroid cartilage Corniculate cartilages (2) - attached to arytenoid
cartilages like a pair of little horns

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

Walls of Larynx
Interior wall has 2 folds on each side, from thyroid to arytenoid cartilages
vestibular folds: superior pair, close glottis during swallowing vocal cords:produce sound

Intrinsic muscles - rotate corniculate and arytenoid

cartilages, which adducts (tightens: high pitch sound) or abducts (loosens: low pitch sound) vocal cords

Extrinsic muscles - connect larynx to hyoid bone,

elevate larynx during swallowing

Action of Vocal Cords

Trachea
Rigid tube 4.5 in. long and 2.5 in. in diameter, anterior to esophagus Supported by 16 to 20 C-shaped cartilaginous rings
opening in rings faces posteriorly towards esophagus trachealis muscle spans opening in rings, adjusts airflow by expanding or contracting

Larynx and trachea lined with ciliated pseudostratified epithelium which functions as mucociliary escalator

Lower Respiratory Tract (trachea thru lungs)

Lungs - Surface Anatomy

Thorax - Cross Section

Bronchial Tree
Primary bronchi (C-shaped rings)
arise from trachea, after 2-3 cm enter hilum of lungs right bronchus slightly wider and more vertical (aspiration)

Secondary (lobar) bronchi (overlapping plates)

branches into one secondary bronchus for each lobe

Tertiary (segmental) bronchi (overlapping plates)

10 right, 8 left bronchopulmonary segment: portion of lung supplied by each

Bronchial Tree 2
Bronchioles (lack cartilage)
have layer of smooth muscle pulmonary lobule: portion ventilated by one bronchiole divides into 50 - 80 terminal bronchioles terminal bronchioles
have cilia , give off 2 or more respiratory bronchioles

respiratory bronchioles (respiratory zone)

divide into 2-10 alveolar ducts

Alveolar ducts - end in alveolar sacs Alveoli - bud from respiratory bronchioles, alveolar
ducts and alveolar sacs

Alveolar Blood Supply

Structure of an Alveolus

Pleurae and Pleural Fluid

Visceral and parietal layers Pleural cavity and fluid Functions
reduction of friction creation of pressure gradient
lower pressure assists in inflation of lungs

compartmentalization
prevents spread of infection

Mechanics of Ventilation
Gas laws (table 22.1)
Boyles law: pressure and volume Charles law: temperature and volume Daltons law: partial pressure Henrys law: gases dissolving in liquids Law of Laplace: alveolar radius

Pressure and Flow

Atmospheric pressure drives respiration
1 atmosphere (atm) = 760 mmHg

Intrapulmonary pressure and lung volume

pressure is inversely proportional to volume
for a given amount of gas, as volume , pressure and as volume , pressure

Pressure gradients
difference between atmospheric and intrapulmonary pressure created by changes in volume of thoracic cavity

Inspiration - Muscles Involved

Diaphragm (dome shaped)
contraction flattens diaphragm composed of skeletal, voluntary muscle

Scalene muscles
fix first pair of ribs

External intercostals
elevate 2 - 12 pairs

Pectoralis minor, sternocleidomastoid and erector spinae muscles

used in deep inspiration

Ptp = Palv - Pip

- at any given volume, Pip is equal and opposite to the inherent elastic recoil of the lung - under physiological conditions, Ptr is always positive

Inspiration - Pressure Changes

intrapleural pressure
as volume of thoracic cavity , visceral pleura clings to parietal pleura

intrapulmonary (Palv) pressure

lungs expand with the visceral pleura

Transpulmonary pressure is more positive Ptp = Palv Pip Inflation of lungs aided by warming of inhaled air A quiet breathe flows 500 ml of air through lungs

Respiratory Pressure & Lung Ventilation

Passive Expiration
During quiet breathing, expiration achieved by elasticity of lungs and thoracic cage (passive process)
some ATP is probably required to relax the muscle (pump Ca2+ back into SR)

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

Forced Expiration
Internal intercostal muscles
depress the ribs

Contract abdominal muscles

intra-abdominal pressure forces diaphragm upward, pressure on thoracic cavity

Pneumothorax
Collection of air or gas in pleural cavity
Ptr = 0 (alveolar pressure = intrapleural pressure) loss of negative intrapleural pressure causes lungs to recoil and collapse

Collapse of lung (or part of lung) is called atelectasis (incomplete extension)

Resistance to Airflow
Pulmonary compliance
distensibility of the lungs; the change in lung volume relative to a given change in transpulmonary pressure decreased in diseases with pulmonary fibrosis (TB)

Bronchiolar diameter
primary control over resistance to airflow bronchoconstriction
triggered by airborne irritants, cold air, parasympathetic stimulation, histamine

bronchodilation
sympathetic nerves, epinephrine

Alveolar Surface Tension

Physical, but slightly erroneous explanation at: http://hyperphysics.phy-astr.gsu.edu/hbase/ptens2.html#alv Thin film of water necessary for gas exchange Problem created by surface tension
resists expansion of alveoli and distal bronchioles
higher surface area means higher potential energy, which is unfavorable surface tension is the work that must be done on the liquid to further increase the surface area

law of Laplace: T = = PR/2 for a sphere R with internal pressure P Pulmonary surfactant (great alveolar cells) disrupts hydrogen bonds, surface tension as passages contract during expiration, surfactant concentration increases preventing alveolar collapse

Respiratory distress syndrome of premature infants

Alveolar Ventilation
Dead air
(http://sprojects.mmi.mcgill.ca/resp/ventilation.htm) fills conducting division of airway, cannot exchange gases

Anatomic dead space = conducting division of airway Physiologic dead space

anatomic dead space + any pathological alveolar dead space

Alveolar ventilation rate

air that actually ventilates alveoli X respiratory rate directly relevant to bodys ability to exchange gases

Ventilation
Measurement Minute ventilation Alveolar ventilation Dead space ventilation Equation = Vt x f = (Vt - VD ) x f = VD x f Meaning Total volume of air entering, L/min Volume of gas reaching alveoli, L/min Volume that remains in conducting zone

Pathological dead space, e.g. in emphysema, reduces alveolar ventilation increasing depth of inspiration (i.e. the tidal volume) is more effective in elevating alveolar ventilation than an equivalent increase in breathing rate f.

Nonrespiratory Air Movements

Functions other than alveolar ventilation
flow of blood and lymph from abdominal to thoracic vessels

Variations in ventilation also serve

speaking, yawning, sneezing, coughing

Valsalva maneuver
take a deep breath, hold it and then contract abdominal muscles; increases pressure in the abdominal cavity to expel urine, feces and to aid in childbirth

Measurements of Ventilation
Spirometer
device a subject breathes into that measures ventilation

Respiratory volumes
tidal volume: air inhaled or exhaled in one quiet breath inspiratory reserve volume: air in excess of tidal inspiration that can be inhaled with maximum effort expiratory reserve volume: air in excess of tidal expiration that can be exhaled with maximum effort residual volume: air remaining in lungs after maximum expiration, keeps alveoli inflated

Lung Volumes and Capacities

Remember the graph

Respiratory Capacities (sums of volumes)

Vital capacity
amount of air that an be exhaled with maximum effort after maximum inspiration; assess strength of thoracic muscles and pulmonary function

Inspiratory capacity
maximum amount of air that can be inhaled after a normal tidal expiration

Functional residual (remaining) capacity

amount of air in lungs after a normal tidal expiration

Total lung capacity

maximum amount of air lungs can contain

Affects on Respiratory Volumes and Capacities

Age: lungs less compliant, respiratory muscles weaken Exercise: maintains strength of respiratory muscles Body size: proportional, big body has large lungs Restrictive disorders: compliance and vital capacity Obstructive disorders: interfere with airflow, expiration
more effort or less complete

Forced expiratory volume: % of vital capacity

exhaled/ time; healthy adult - 75 to 85% in 1 sec

Minute respiratory volume: Total V x respiratory rate,

at rest 500 x 12 = 6 L/min; maximum: 125 to 170 L/min

Neural Control of Ventilation

Breathing depends on repetitive stimuli from brain Neurons in medulla oblongata and pons control unconscious breathing Voluntary control provided by the motor cortex Inspiratory neurons: fire during inspiration Expiratory neurons: fire during forced expiration Fibers travel down spinal cord to lower motor neurons, fibers of phrenic nerve go to diaphragm and intercostal nerves go to intercostal muscles

Respiratory Control Centers

Two respiratory nuclei in medulla oblongata
inspiratory center (dorsal respiratory group)
more frequently they fire, more deeply you inhale longer duration they fire, breath is prolonged, slow rate

expiratory center (ventral respiratory group)

involved in forced expiration

Pons
pneumotaxic center
sends continual inhibitory impulses to inspiratory center, as impulse frequency rises, breathe faster and shallower

apneustic center
sends continual stimulatory impulses to inspiratory center

Respiratory Control Centers

Afferent Connections to Brainstem

Input from limbic system and hypothalamus
respiratory effects of pain and emotion

Input from chemoreceptors

brainstem and arteries monitor blood pH, CO2 and O2 levels

Input from airways and lungs

response to inhaled irritants
stimulate vagal afferents to medulla, results in bronchoconstriction or coughing

inflation reflex
excessive inflation triggers this reflex, stops inspiration

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

Composition of Air
Mixture of gases, each contributes its partial pressure, (at sea level 1 atm. of pressure = 760 mmHg)
nitrogen constitutes 78.6% of the atmosphere, PN2 = 78.6% x 760 mmHg = 597 mmHg PO2 = 159, PH2O = 3.7, PCO2 = 0.3 mmHg
(597 + 159 + 3.7 + 0.3 = 760)

Partial pressures determine rate of diffusion of gas and gas exchange between blood and alveolus Alveolar air
humidified, exchanges gases with blood, mixes with residual air contains: PN2 = 569, PO2 = 104, PH2O = 47, PCO2 = 40 mmHg

Diffusion of gases (from respiratory physiology)

a gas diffuses from a region where that particular gas has higher partial pressure to a region of lower partial pressure different from bulk flow in conducting airways, where all gases move from low to high total pressure higher T faster molecular motion faster diffusion rate by the time air reaches alveoli, bulk flow air velocity virtually ceases due to large effective cross area (Av = const.)
oxygen now moves according to its partial pressure gradient only free or unbound gas can contribute to the partial pressure of that gas in air or liquid which contains the gas the assumption is that undissolved ideal gas does not interact with the liquid, so can disregard the liquid environment gas above and gas undissolved in the liquid will eventually reach equilibrium, where partial pressures in and out become equal (e.g. 0.25 sec for O2 to equilibrate)

Diffusion of O2
Henry's law: the amount of a gas absorbed by a liquid with which it does not combine chemically is directly proportional to the partial pressure of the gas to which the liquid is exposed and the solubility of the gas in the liquid O2 must dissolve in and diffuse through the thin layer of surfactant, the alveolar epithelium, the interstitium, and the capillary endothelium it then diffuses through the plasma (where some of it remains) and the majority enters the erythrocyte, and combines with Hb. oxygen is carried away from the lung by bulk blood flow and is released in the tissues (by a similar process) the reverse process occurs with CO2

Diffusion pathway for O2

Cross section of a pulmonary capillary. An erythrocyte (EC) is seen within the capillary. C = capillary; EN = capillary endothelial cell (note its large nucleus); EP = alveolar epithelial cell; IN = interstitial space; BM = basement membrane; FB = fibroblast processes; 2,3,4 = diffusion pathway through the alveolar-capillary barrier, the plasma, and the erythrocyte, respectively.

Ficks law describes the rate of diffusion across the alveolar-capillary barrier
Vgas = volume of gas diffusing through the tissue barrier per time, mL/min A = surface area of the barrier available for diffusion D = diffusion coefficient, or diffusivity, of the particular gas in the barrier T = thickness of the barrier or the diffusion distance P1 P2 = partial pressure difference of the gas across the barrier

A of blood-gas barrier is about 70 m2 in a healthy adult individual

during exercise more area is perfused and ventilated, as more capillaries are recruited during hemorrhage, capillaries may be derecruited and surface area available for diffusion may decrease

T of alveolar-capillary barrier is about 05-0.2 mm

interstitial fibrosis or edema can increase the thickeness of the barrier and decrease diffusion

at a given T lighter molecules diffuse faster (recall Grahams law)

according to Grahams law O2 should diffuse 1.2x faster than CO2 but since CO2 is 24 more soluble it should diffuse 24x(1/1.2) = 20 times faster partial pressures are taken into account in next slides

Note: This alveolar partial pressure is different for each of the three gases (different yscale on the graph for each gas): depends on its concentration in the inspired gas mixture and on how rapidly it is removed by the pulmonary capillary blood. Consider each gas as though it were acting independently of the others.

Alveolar Gas Exchange

Partial pressures equilibrate rapidly with the alveolar partial pressures Time required for oxygen to equilibrate = 0.25 sec RBC transit time at resting cardiac output = 0.75 sec to pass through alveolar capillary RBC transit time with vigorous exercise = 0.3 sec CO has very high affinity for Hb. A lot of CO inters the blood in 0.75, but most of it combines with Hb and thus does not contribute to the partial pressure in the capillary, since it is not physically dissolved in the blood

O2 initially combines with Hb, partial pressure in artery increases slowly. As Hb becomes saturated with the gas, partial pressure rapidly rises and no further transfer (diffusion) of oxygen occurs (after about 0.25 sec) Perfusion rate during exercise may be increased up to 0.25 sec in the capillary, without adverse perfusion limitation At high altitude, where alveolar O2 partial pressure is lower, diffusion rate is reduced and abnormal individuals may be subject to diffusion limitation of oxygen transfer

Diffusion of CO2
diffusivity of carbon dioxide is about 20 times larger partial pressure differential is only 5 mm Hg, compared to 60 mm Hg for oxygen as a result, CO2 takes about 0.25 sec to diffuse, similar to O2 transfer can be limited by perfusion rate (too high) or increased diffusion barrier

Oxygen transfer
Withour Hb, the physically dissolved O2 would not be sufficient to meet the tissue demands for O2 the cardiac output would have to be 83L/min !!! under extreme exercise we can get only 25L/min with Hb, our oxygen-carrying capacity increases dramatically:
20.1 mL O2/100 mL of blood (for about 15g of Hb) the binding is reversible and is determined by the partial pressure of oxygen in the plasma that will enter the erythrocyte (excluding the dissolved part)

Partial pressure gradients of Gases

Partial pressure gradients affect diffusion rates

Lung Disease Affects Gas Exchange

membrane thickness

surface area

Perfusion (blood flow) Adjusts to Changes in Ventilation

Ventilation Adjusts to Changes in Perfusion

Oxygen Transport
Concentration in arterial blood
20 ml/dl, (98.5% bound to hemoglobin, 1.5% dissolved)

Binding to hemoglobin
each heme group of 4 globin chains may bind O2 oxyhemoglobin (HbO2 ), deoxyhemoglobin (HHb)

Oxyhemoglobin dissociation curve

relationship between hemoglobin saturation and PO2 is not a simple linear one after binding with O2, hemoglobin changes shape to facilitate further uptake (positive feedback cycle)

Oxyhemoglobin Dissociation Curve

Hb saturation is determined by the partial pressure of O2 Largest affinity at highest partial pressure values

Carbon Dioxide Transport

As carbonic acid - 90%
CO2 + H2O H2CO3 HCO3- + H+

As carbaminohemoglobin (HbCO2)- 5% binds to amino groups of Hb (and plasma proteins) As dissolved gas - 5% Alveolar exchange of CO2
carbonic acid - 70% carbaminohemoglobin - 23% dissolved gas - 7%

Systemic Gas Exchange (in the tissues)

CO2 loading
carbonic anhydrase in RBC catalyzes chloride shift keeps reaction proceeding, exchanges HCO3- for Cl(H+ binds to hemoglobin)
CO2 + H2O H2CO3 HCO3- + H+

O2 unloading

H+ binding to HbO2 deacreases its affinity for O2 this facilates the release of O2 to the tissue (Bohr effect) Hb arrives 97% saturated, leaves 75% saturated - venous reserve utilization coefficient amount of oxygen Hb has released 22%

more CO2 gives more H+, shifting eq. to the left and releasing more O2 (Bohr effect). Taking away H+ also shifts the bicarbonate eq. to the formation of more bicarbonate. Releasing more oxygen creates more HHb, which binds more CO2 for transfer (Haldane effect)

deoxyhemoglobin (Hb and its protonated form, HHb) binds CO2 better than HbO2 , Hb is a stronger base than HbO2

Alveolar Gas Exchange

Reactions are reverse of systemic gas exchange CO2 unloading
as Hb loads O2 its affinity for H+ decreases, H+ dissociates from Hb and binds to HCO3- (which diffuses back into RBC from plasma), CO2 + H2O H2CO3 HCO3- + H+ reverse chloride shift keeps reaction proceeding, exchanges Cl- for HCO3 free CO2 generated diffuses into alveolus to be exhaled

Alveolar Gas Exchange

Adjustment to Metabolic Needs of Tissues

Factors affecting O2 unloading (HbO2 releases O2)
ambient PO2: active tissue has PO2 , O2 is released temperature: active tissue has increased temp, O2 is released (see next slide) Bohr effect: active tissue has CO2, which raises H+ and lowers pH, O2 is released (see following slide) bisphosphoglycerate (BPG): RBCs produce this as a metabolic intermediate in glycolysis, BPG binds to Hb and causes HbO2 to more easily release O2 body temp (fever), TH, GH, testosterone, and epinephrine all raise BPG and cause O2 unloading

Oxygen Dissociation & Temperature

Active tissue - more O2 released

PO2 (mmHg)

Oxygen Dissociation & pH

Active tissue - more O2 released

Bohr effect: release of O2 in response to low pH

Adjustment to Metabolic Needs of Tissues

Factors affecting CO2 loading
Haldane effect: Deoxygenation of the blood increases its ability to carry carbon dioxide high level of Hb (as in active tissue) enables blood to transport more CO2
HHb binds stronger to CO2 than HbO2 (more CO2 is taken up as carbamino cmpd) Hb is a stronger base than HbO2 and thus binds more H+, shifting the equilibrium to the right CO2 + H2O HCO3- + H+ reaction to the right

Blood Chemistry and Respiratory Rhythm

Chemoreceptors monitor pH, PCO2, PO2 of body fluids
peripheral chemoreceptors
aortic bodies - signals medulla oblongata by vagus nerves carotid bodies - signals medulla by glossopharyngeal nerves

central chemoreceptors (surface of medulla)

primarily monitor pH of CSF

Peripheral Chemoreceptor Pathways

Effects of Hydrogen Ions

pH of CSF: most powerful respiratory stimulus Respiratory acidosis (pH < 7.35)
caused by failure of pulmonary ventilation

hypercapnia PCO2 > 43 mmHg CO2 easily crosses blood-brain barrier, in CSF the CO2 reacts with water and releases H+, central chemoreceptors strongly stimulate inspiratory center corrected by hyperventilation, pushes reaction to the left by blowing off CO2 CO2 (expired) + H2O H2CO3 HCO3- + H+

Effects of Hydrogen Ions

Respiratory alkalosis (pH > 7.35)
hypocapnia PCO2 < 37 mmHg corrected by hypoventilation, pushes reaction to the right CO2 + H2O H2CO3 HCO3- + H+ H+, lowers pH to normal

pH imbalances can have metabolic causes

diabetes mellitus: fat oxidation causes ketoacidosis, can be compensated for by Kussmaul respiration, (deep rapid breathing)

Carbon Dioxide
Indirect effects
through pH as seen previously

Direct effects
CO2 (hypercapnia) may directly stimulate peripheral chemoreceptors and trigger ventilation more quickly than central chemoreceptors

Oxygen
Usually little effect Chronic hypoxemia, PO2 < 60 mmHg, can significantly stimulate ventilation
emphysema, pneumonia high altitudes after several days

Oxygen Imbalances
Hypoxia
hypoxemic hypoxia (hypoxemia) low oxygen content in the blood
usually due to inadequate pulmonary gas exchange (thicker barrier in cystic fibrosis) high altitudes, drowning, aspiration, respiratory arrest, degenerative lung diseases, CO poisoning

ischemic hypoxia - inadequate circulation anemic hypoxia anemia circulatory problem with blood circulation to the tissue histotoxic hypoxia tissue cannot utilize O2 e.g. cyanide poisons the metabolic machinery cyanosis - blueness of skin primary effect of hypoxia is tissue necrosis, organs with high metabolic demands affected first

Oxygen Imbalances
Oxygen excess
oxygen toxicity: pure O2 breathed at 2.5 atm or greater
generates free radicals and H2O2, destroys enzymes, damages nervous tissue, seizures, coma death

hyperbaric oxygen
formerly used to treat premature infants, caused retinal damage, discontinued

Chronic Obstructive Pulmonary Diseases (COPD)

Asthma - allergen triggers histamine release, intense
bronchoconstriction

Other COPDs usually associated with smoking

chronic bronchitis
cilia immobilized and in number, goblet cells enlarge and produce excess mucus, sputum formed (mixture of mucus and cellular debris) which is ideal growth media for bacteria, chronic infection; bronchial inflammation ensues

emphysema
alveolar walls break down, much less respiratory membrane for gas exchange, lungs fibrotic and less elastic, air passages collapse and obstruct outflow of air, air trapped in lungs

Other 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 heart due to obstruction of pulmonary circulation

Smoking and Lung Cancer

Lung cancer accounts for more deaths than any other form of cancer
most important cause is smoking (15 carcinogens)

Squamous-cell carcinoma (most common)

begins with transformation of bronchial epithelium into stratified squamous dividing cells invade bronchial wall, cause bleeding lesions dense swirls of keratin replace functional respiratory tissue

Lung Cancer
Adenocarcinoma
originates in mucous glands of lamina propria

Small-cell (oat cell) carcinoma

least common, most dangerous originates in primary bronchi, invades mediastinum, metastasizes quickly

Progression of Lung Cancer

90% of lung tumors originate in primary bronchi Tumor invades bronchial wall, compresses airway and may cause atelectasis Often first sign is coughing up blood Metastasis is rapid and has usually occurred by time of diagnosis
common sites: pericardium, heart, bones, liver, lymph nodes and brain

Prognosis poor
7% of patients survive 5 years after diagnosis

Healthy Adult Lung