Respiratory

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Chapter 16
Respiratory Physiology
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Respirations

• Encompasses 3 related functions ventilation, gas
  exchange, and O2 utilization (cellular
  respiration)
• Ventilation (breathing) moves air in and out of
  lungs
• External respiration gas exchange between lungs
  and blood
• Internal respiration gas exchange between blood
  and tissues, and O2 use by tissues
• Gas exchange is passive via diffusion

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Structure of Respiratory System

• Air passes from mouth to trachea to right and
  left bronchi to bronchioles to terminal
  bronchioles to respiratory bronchioles to alveoli

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Structure of Respiratory System continued

• Gas exchange occurs only in respiratory
  bronchioles and alveoli ( respiratory zone)
• All other structures constitute the conducting
  zone
• Alveoli are on and clustered at ends of
  respiratory bronchioles, like units of honeycomb

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Structure of Respiratory System

• Gas exchange occurs across the 300 million
  alveoli
• Only 2 thin cells with a basement membrane are
  between lung air and blood 1 alveolar and 1
  endothelial cell with a common basal lamina

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Physical Aspects of Ventilation

• Ventilation results from pressure differences
  induced by changes in lung volumes
• Air moves from areas of higher pressure to areas
  of lower pressure (like diffusion)
• Compliance, elasticity, and surface tension of
  lungs influence ease of ventilation

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Intrapulmonary and Intrapleural Pressures

• Visceral and parietal pleurae normally adhere to
  each other so that lungs remain in contact with
  chest walls
• Lungs expand and contract with thoracic cavity

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Intrapulmonary and Intrapleural Pressures
continued

• Intrapleural space contains a thin layer of
  lubricating fluid (pleural fluid)

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Intrapulmonary and Intrapleural Pressures
continued

• Intrapulmonary pressure gas pressure in lung
  alveoli
• Intrapleural pressure pressure within pleural
  cavity

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Boyles Law (P 1/V)

• Implies that changes in intrapulmonary pressure
  occur as a result of changes in lung volume
• Pressure of gas is inversely proportional to
  volume
• As volume of container is decreased, the pressure
  inside increases (and vice versa)
• Increases in lung volume decreases intrapulmonary
  pressure causing inspiration
• Decrease in lung volume raises intrapulmonary
  pressure causing expiration

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Compliance

• How easily lung expands with pressure
• (ie stretchability, distension)
• Is reduced by factors that cause resistance to
  distension (pulmonary fibrosis, emphysema, tumor)

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Elasticity

• Is tendency to return to initial size following
  distension
• Due to high content of elastin proteins in lung
  tissue
• Elastic tension increases during inspiration and
  is reduced by recoil during expiration

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Surface Tension (ST)

• And elasticity are forces that promote alveolar
  collapse and resist distension
• Normally always a thin film of fluid on inner
  alveolar surface
• This film causes Surface Tension because H20
  molecules are attracted to other H2O molecules
• Force of ST is directed inward, raising pressure
  in alveoli
• Potentially causing collapse

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Surface Tension continued

• Law of Laplace states that pressure in alveolus
  is directly proportional to ST and inversely to
  radius of alveoli
• Thus, pressure in smaller alveoli would be
  greater than in larger alveoli, if ST were the
  same in both

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Surfactant

• Consists of phospholipids secreted by Type II
  alveolar cells
• Lowers ST by getting between H2O molecules,
  reducing their ability to attract each other via
  hydrogen bonding (ie
• surfactant interferes with hydrogen bonding in
  water)

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Surfactant continued

• Prevents ST from collapsing alveoli
• Surfactant secretion begins in late fetal life
• Premies are often born with immature surfactant
  system ( Respiratory Distress Syndrome or RDS)
• Have trouble inflating lungs because ST is too
  high

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Mechanics of Breathing

• Pulmonary ventilation consists of inspiration (
  inhalation) and expiration ( exhalation)
• Accomplished by alternately increasing and
  decreasing volumes of thorax and lungs

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Quiet Breathing

• Inspiration occurs mainly because diaphragm
  contracts, increasing thoracic volume vertically
• External intercostal contraction contributes a
  little by raising ribs, increasing thoracic
  volume laterally
• Air flows into the lungs when alveolar pressure
  drops below atmospheric pressure
• Expiration is due to passive recoil

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Mechanics of Pulmonary Ventilation
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Pulmonary Function Tests

• Assessed clinically by spirometry, a method that
  measures volumes of air moved during inspiration
  and expiration
• Spirographs are the instruments that measure
• lung volumes

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Pulmonary Function Tests continued

• Tidal volume is amount of air ventilated during
  quiet breathing
• Vital capacity is amount of air that can be
  forcefully exhaled following a maximum inhalation
• sum of inspiratory reserve, tidal volume, and
  expiratory reserve

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Pulmonary DisordersRestrictive Disorders

• Are characterized by reduced vital capacity but
  with normal forced vital capacity (ie lungs
  cannot expand enough but the airways are clear)
• e.g. pulmonary fibrosis, tumor, emphysema

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Obstructive Disorders

• Have normal vital capacity but expiration is
• inhibited
• e.g. asthma
• Diagnosed by tests, such as forced expiratory
  volume, that measures rate of expiration
• Treated with Parasympathetic antagonists

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Pulmonary Disorders continued

• Asthma results from episodes of obstruction of
  air flow thru bronchioles
• Caused by inflammation, mucus secretion, and
  bronchoconstriction
• Provoked by allergic reactions that release IgE
  antibodies by exercise by breathing cold, dry
  air or by aspirin

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Pulmonary Disorders continued

• Emphysema is a chronic, progressive condition
  that destroys alveolar tissue, resulting in
  fewer, larger alveoli
• Reduces surface area for gas exchange and ability
  of bronchioles to remain open during expiration
• Commonly occurs in long-term smokers
• Cigarette smoking stimulates release of
  inflammatory cytokines which attract macrophages
  and leukocytes that secrete enzymes that destroy
  tissue

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Pulmonary Disorders continued

• Chronic Obstructive Pulmonary Disease (COPD)
  involves chronic inflammation accompanied by
  narrowing of airways and destruction of alveolar
  walls
• Most people with COPD are smokers
• Is fifth leading cause of death

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Pulmonary Disorders continued

• Sometimes lung damage leads to pulmonary fibrosis
  instead of emphysema
• Characterized by accumulation of fibrous
  connective tissue in lungs
• Occurs from inhalation of particles lt6?m in size,
  such as in black lung disease (anthracosis) from
  coal dust or from smoking

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Partial Pressure of Gases

• Partial pressure is pressure that a particular
  gas in a mixture exerts independently
• Daltons Law states that total pressure of a gas
  mixture is the sum of partial pressures of each
  gas in mixture
• Atmospheric pressure at sea level is 760 mm Hg
• PATM PN2 PO2 PCO2 PH2O 760 mm Hg

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Gas Exchange in Lungs

• Is driven by differences in partial pressures of
  gases between alveoli and capillaries

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Gas Exchange in Lungs continued

• Is facilitated by enormous surface area of
  alveoli, short diffusion distance between
  alveolar air and capillaries, and tremendous
  density of capillaries

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Partial Pressures of Gases in Blood

• When blood and alveolar air are at equilibrium
  the amount of O2 in blood reaches a maximum value
  
• Henrys Law says that this value depends on
  solubility of O2 in blood (a constant),
  temperature of blood (a constant), and the
  partial pressure of O2
• So the amount of O2 dissolved in blood depends
  directly on its partial pressure (PO2), which
  varies with altitude (higher PO2-more dissolved
  in solution)

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Blood PO2 and PCO2 Measurements

• Provide good index of lung function
• At normal PO2 arterial blood has about 100 mmHg
  PO2
• PO2 is about 40 mmHg in systemic veins
• PCO2 is 46 mmHg in systemic veins

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Brain Stem Respiratory Centers

• Automatic breathing is generated by a rhythmicity
  center in medulla oblongata
• Consists of inspiratory neurons that drive
  inspiration and expiratory neurons that inhibit
  inspiratory neurons

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Brain Stem Respiratory Centers continued

• Inspiratory neurons stimulate spinal motor
  neurons that innervate respiratory muscles
• Expiration is passive and occurs when inspiratory
  neurons are inhibited

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Pons Respiratory Centers

• Activities of medullary rhythmicity center are
  influenced by centers in pons
• Apneustic center promotes inspiration by
  stimulating inspiratories in medulla
• Pneumotaxic center antagonizes apneustic center,
  inhibiting inspiration

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Chemoreceptors

• Automatic breathing is influenced by activity of
  chemoreceptors that monitor blood PCO2, PO2, and
  pH
• Central chemoreceptors are in medulla
• Peripheral chemoreceptors are in large arteries
  near heart (aortic bodies) and in carotids
  (carotid bodies)

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Effects of Blood PCO2 and pH on Ventilation

• Chemoreceptors modify ventilation to maintain
  normal CO2, O2, and pH levels
• PCO2 is most crucial because of its effects on
  blood pH
• H2O CO2 ? H2CO3 ? H HCO3-

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Effects of Blood PCO2 and pH on Ventilation
continued

• Central (ie brain) chemoreceptors are
  responsible for greatest effects on ventilation
• H can't cross BBB but CO2 can, which is why it
  is monitored and has greatest effects
• Rate and depth of ventilation is adjusted to
  maintain arterial PCO2 of 40 mm Hg
• Peripheral chemoreceptors do not respond to PCO2,
  only to H levels

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Hemoglobin (Hb) and O2 Transport

• Each Hb has 4 globin polypeptide chains and 4
  heme groups that bind O2
• Each heme has a ferrous ion that can bind 1 O2
• So each Hb can bind 4 O2s
• Heme can also bind carbon monoxide

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Hemoglobin (Hb) and O2 Transport continued

• Most O2 in blood is bound to Hb inside RBCs as
  oxyhemoglobin
• Each RBC has about 280 million molecules of Hb
• Hb greatly increases O2 carrying capacity of blood

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Hemoglobin (Hb) and O2 Transport

• Methemoglobin contains ferric iron (Fe3) -- the
  oxidized form
• Lacks electron to bind with O2
• Blood normally contains a small amount
• Carboxyhemoglobin is heme combined with carbon
  monoxide
• Bond with carbon monoxide is 210 times stronger
  than bond with oxygen

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Oxyhemoglobin Dissociation Curve

• Gives of Hb sites that have bound O2 at
  different PO2s
• Reflects loading and unloading of O2
• Differences in saturation in lungs and tissues
  are shown at right
• In steep part of curve, small changes in PO2
  cause big changes in saturation

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Oxyhemoglobin Dissociation Curve

• Is affected by changes in Hb-O2 affinity caused
  by pH and temperature
• Affinity decreases when pH decreases (Bohr
  Effect) or temp increases
• Occurs in tissues where temp, CO2 and acidity are
  high
• Causes Hb-O2 curve to shift right and more
  unloading of O2

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Effect of 2,3 DPG on O2 Transport2,3
Diphosphoglyceric acid

• RBCs have no mitochondria cant perform aerobic
  respiration
• 2,3-DPG is a byproduct of glycolysis in RBCs
• Its production is increased by low O2 levels
• Causes Hb to have lower O2 affinity, shifting
  curve to right

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Myoglobin

• Has only 1 globin binds only 1 O2
• Has higher affinity for O2 than Hb is shifted to
  extreme left
• Releases O2 only at low PO2
• Serves in O2 storage, particularly in heart
  during systole

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CO2 Transport

• CO2 transported in blood as dissolved CO2 (10),
  carbaminohemoglobin (20), and bicarbonate ion,
  HCO3-, (70)
• In RBCs carbonic anhydrase catalyzes formation of
  H2CO3 from CO2 H2O

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Chloride Shift

• High CO2 levels in tissues causes the reaction
  CO2 H2O ? H2CO3 ? H
  HCO3- to shift right in RBCs
• Results in high H and HCO3- levels in RBCs
• H is buffered by proteins
• HCO3- diffuses down concentration and charge
  gradient into blood causing RBC to become more
• So Cl- moves into RBC (chloride shift)

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Chloride Shift
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Acid-Base Balance in Blood

• Blood pH is maintained within narrow pH range by
  lungs and kidneys (normal 7.4)
• Most important buffer in blood is bicarbonate
• H2O CO2 ? H2CO3 ? H HCO3-
• Excess H is buffered by HCO3-
• Kidney's role is to excrete H into urine

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Acid-Base Balance in Blood continued

• Acidosis is when pH lt 7.35 alkalosis is pH gt
  7.45
• Respiratory acidosis caused by hypoventilation
• Causes rise in blood CO2 and thus carbonic acid
• Respiratory alkalosis caused by hyperventilation
• Results in too little CO2

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Acid-Base Balance in Blood continued

• Metabolic acidosis results from excess of
  nonvolatile acids
• e.g. excess ketone bodies in diabetes or loss of
  HCO3- (for buffering) in diarrhea
• Hyperventilation is a symptom
• Metabolic alkalosis caused by too much HCO3- or
  too little nonvolatile acids (e.g. from vomiting
  out stomach acid)

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Acid-Base Balance in Blood continued

• Metabolic acidosis results from excess of
  nonvolatile acids
• E.g. excess ketone bodies in diabetes or loss of
  HCO3- (for buffering) in diarrhea
• Metabolic alkalosis caused by too much HCO3- or
  too little nonvolatile acids (e.g. from vomiting
  out stomach acid)

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Respiratory Acid-Base Balance

• Ventilation usually adjusted to metabolic rate to
  maintain normal CO2 levels
• With hypoventilation not enough CO2 is breathed
  out in lungs
• Acidity builds, causing respiratory acidosis
• With hyperventilation too much CO2 is breathed
  out in lungs
• Acidity drops, causing respiratory alkalosis

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